STAPH PROTEIN A COWAN I RESOURCE PAGE - DR. JOHN
RAYMOND BAKER,DC
This page is part of the
FelineLeukemia.Info Network, and as, with all my websites,
Dedicated to the Memory of DUMPLIN BAKER
--- WHAT IS THIS
STAPH PROTEIN A WHICH IS USED in the treatment of FELINE LEUKEMIA AND
NEOPLASMS ASSOCIATED WITH , OR CAUSED BY FeLV.
--- WHAT IS STAPH A COWAN I ?
---
HOW DOES THIS RELATE TO THE IMMUNOPATHOLOGY INDUCED BY THE FELINE LEUKEMIA VIRUS
?
---PLACES
TO GET STAPH PROTEIN A and the PROTOCOL
(
HOME - to FELINELEUKEMIA.INFO )
From FelineLeukemia.org, I found this list
"- Treatment of feline leukemia and reversal of FeLV by ex vivo removal of IgG:
a preliminary report. Jones, Yoshida, Ladiges Kenny. Cancer. 1980 Aug
15;46(4):675 84.
http://www.ncbi.nlm.nih.gov/pubmed/6249487?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Remission of lymphoma leukemia in cats following ex vivo immunosorption
therapy using Staphylococcus protein A. Day, Engelman, Liu, Trang, Good. J Biol
Response Mod. 1984;3(3):278 85. No abstract available.
http://www.ncbi.nlm.nih.gov/pubmed/6086846?ordinalpos=12&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Appearance of cytotoxic antibody to viral gp70 on feline lymphoma cells (FL
74) in cats during ex vivo immunoadsorption therapy: quantitation,
characterization, and association with remission of disease and disappearance of
viremia. Liu, Engelman, Trang, Hau, Good, Day. Proc Natl Acad Sci U S A. 1984
Jun;81(11):3516 20.
http://www.ncbi.nlm.nih.gov/pubmed/6328520?ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Remission of leukemia and loss of feline leukemia virus in cats injected
with Staphylococcus protein A: association with increased circulating interferon
and complement dependent cytotoxic antibody. Liu, Good, Trang, Engelman, Day.
Proc Natl Acad Sci U S A. 1984 Oct;81(20):6471 5.
http://www.ncbi.nlm.nih.gov/pubmed/6208551?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Clinicopathologic responses in cats with feline leukemia virus associated
leukemia lymphoma treated with staphylococcal protein A. Engelman, Tyler, Trang,
Liu, Good, Day. Am J Pathol. 1985 Mar;118(3):367 78.
http://www.ncbi.nlm.nih.gov/pubmed/2983560?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Antitumor activity of protein A administered intravenously to pet cats with
leukemia or lymphosarcoma. Harper, Sjöquist Hardy, Jones. Cancer. 1985 May
1;55(9):1863 7.
http://www.ncbi.nlm.nih.gov/pubmed/2983866?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Changing manifestations of a chronic feline haematopoietic proliferative
disease during immunotherapy with staphylococcal protein A. Engelman, Tyler,
Mosier, Good, Day. J Comp Pathol. 1986 Mar;96(2):177 88.
http://www.ncbi.nlm.nih.gov/pubmed/3009564?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Clearance of retroviremia and regression of malignancy in cats with leukemia
lymphoma during treatment with staphylococcal protein A. Engelman, Good, Day.
Cancer Detect Prev. 1987;10(5 6):435 44.
http://www.ncbi.nlm.nih.gov/pubmed/3032440?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Immunotherapy for feline leukemia, using staphylococcal protein A or
heterologous interferons: immunopharmacologic actions and potential use. Weiss.
J Am Vet Med Assoc. 1988 Mar 1;192(5):681 4. Review. No abstract available.
http://www.ncbi.nlm.nih.gov/pubmed/2453494?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Hitt, McCaw. FeLV Infection, Hemolytic Anemia and Hypocellular Bone Marrow in
a Cat: Treatment with Protein A and Prednisone. Can Vet J. 1988 Sep;29(9):737
739. No abstract available.
http://www.ncbi.nlm.nih.gov/pubmed/17423122?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Remission of FeLV associated lymphosarcoma and persistent viral infection
after extracorporeal immunoadsorption of plasma using staphylococcal protein A
columns: details of immune response. Snyder, Reed, Jones. Semin Hematol. 1989
Apr;26(2 Suppl 1):25 30.
http://www.ncbi.nlm.nih.gov/pubmed/2543084?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
- Biological effects of staphylococcal protein A immunotherapy in cats with
induced feline leukemia virus infection. Lafrado, Mathes, Zack, Olsen. Am J Vet
Res. 1990 Mar;51(3):482 6.
http://www.ncbi.nlm.nih.gov/pubmed/1690524?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
-Immunomodulation therapy for feline leukemia virus infection. McCaw, Boon,
Jergens, Kern, Bowles, Johnson. J Am Anim Hosp Assoc. 2001 Jul Aug;37(4):356 63.
http://www.ncbi.nlm.nih.gov/pubmed/11450836?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum"
----End of Quote-----
Having lost my dear friend and furry child Dumplin, a pure white, very much loved Turkish Angora to this hated disease, I am trying my best to find all the information about what has proven to work against FeLV and the associated cancers such as lymphosarcoma (the one Dumplin had, and the most commonly caused cancer , i.e. caused by the oncovirus, FeLV).
There are some researchers doing work in the area of FeLV,
basic facts , transmission, etc.
To some extent, the model of treatment of a cat who is infected with FeLV is
copied to some extent
from the human model of AIDS and cancer. The HIV (so-called "AIDS" virus) is a
retrovirus, as
is FeLV. They both are immunosuppressive, and expose those infected to
development of so-called
"opportunistic infections" and certain cancers. Opportunistic infections, are
usually those infections that a normal, healthy individual with a strong immune
system would not develop, but in those who are immunologically compromised, the
disease can take hold and wreak havoc.
What is FeLV? FeLV is a virus, a retrovirus which can
enter a cell and take over the cell, much
like someone can steal your car, and then use it as they will.
What is Staph Protein
A ?
Staph is Staphylococcus aureus, a virulent bacterial infection, so named because
of the
yellowish golden discharge it produces (i.e. "aureus" from the Latin for Gold).
What is the Protein A part ? From
Wikipedia, we read :
" Protein A is a 40-60 kDa MSCRAMM surface protein originally
found in the cell wall of the bacteria
Staphylococcus aureus. It is encoded by the spa gene
and its regulation is controlled by DNA topology, cellular osmolarity, and a two-component
system called ArlS-ArlR. It has
found use in biochemical research because of its ability to bind immunoglobulins.
It binds proteins from many of mammalian species, most notably IgG’s.
It binds with the Fc
region of immunoglobulins through
interaction with the heavy chain. The result of this type of interaction is
that, in serum, the bacteria will bind IgG molecules in the wrong orientation
(in relation to normal antibody function)
on their surface which disrupt sopsonization and phagocytosis."
In the research performed in the area of treatment of FeLV, the ability of Staph
Protein A to bind
to the Circulating Immune Complexes, and the Immunoglobulin G, appears to be the
action which can cause FeLV to go into remission , and help to clear or destroy
cancers
like LSA (lymphosarcoma).
Another definition of Staph Protein A is as follows (from
National Cancer Institute) .
"staphylococcus
aureus protein A
A protein that resides in the microbial wall of staphylococcus aureus and
interferes with opsonization by binding to the Fc portion of immunoglobulin. The
protein has a deleterious effect on the epithelial cells that line the
respiratory tract, and plays a role in the induction of pneumonia. Protein A
also initiates polymorphonuclear cell migration into airway passages via TNFR1
activation. Check for active
clinical trialsor closed
clinical trials using this agent.
(NCI
Thesaurus)"
In much of the
research done with the Staph Protein A, they use Staph Protein A Cowan I.
In one study, it was found that in humans, the Staph Protein A Cowan I activates
basophils to
release histamine. Histamine causes inflammation, with the resulting increase of
white blood
cell phagocytic activity.
See this study on MECHANISM of ACTIVATION OF HUMAN BASOPHILS
by Staphylococcus Aureus Cowan I.
" We investigated the capacity of
Staphylococcus aureus Cowan 1 and S. aureus Wood 46 to induce histamine release
from human basophils in vitro. S. aureus
Cowan
1 (105 to
107/ml), which synthesizes protein A (Staph
A), stimulated the release of histamine from basophils, whereas S.
aureus Wood
46 (105 to
2 x
107/ml), which does not synthesize Staph A,
did not
induce histamine secretion. Soluble Staph A (l0-3
to 10
,ig/ml), but
not
staphylococcal enterotoxin A, induced histamine secretion from human basophils.
Staph A binds through its
classical site to
the Fc region of human immunoglobulin G (IgG) and
through its alternative site to
the Fab portion of the different human
immunoglobulins."
What is "COWAN
I"?
Staphylococcus aureus Cowan I (SAC), is a protein A-positive Staphylococcal
strain, and is a potent and consistent inducer of IgM rheumatoid factor
production by normal human peripheral blood mononuclear cells.
Here
is an article about the Staph A Cowan I.
Here is the complete article in PDF format. The Abstract of the article
says:
"These studies demonstrate that Staphylococcus aureus Cowan I (SAC), a protein
A-positive Staphylococcal strain, is a potent and consistent inducer of IgM
rheumatoid factor production by normal human peripheral blood mononuclear cells.
The frequency and magnitude of this response greatly exceeded that of parallel
cultures stimulated with pokeweed mitogen or the protein A-negative S. aureus
Wood strain, although all three agents induced a similar amount of total IgM.
Cell fractionation studies indicated that SAC-induced IgM rheumatoid factor is T
cell-dependent. The striking ability of SAC to induce IgM rheumatoid factor may
relate to its protein A content, since cultures stimulated with protein
A-coupled sepharose beads also consistently produced this autoantibody. Thus SAC
is a new probe of in vitro IgM rheumatoid factor production and its use has
provided further evidence that most healthy individuals harbor precursors of IgM
rheumatoid factor secreting cells. Unlike other polyclonal activators, SAC is
unique in its capacity to bind immunoglobulin, a property that may account for
its prominent anti-IgG inducing capacity."
Does Staph Protein A have an effect on neoplasms
(cancers) ?
Here
is a good article about this topic.
Effects of Plasma Treatment with Purified Protein A and Staphylococcus
aureus Cowan I on Spontaneous
Animal Neoplasms1
"
Departments of Small Animal Clinical Sciences [J. S. K.] and Pathobiology [T. D. O.], College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108, and Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455 [R. F. B., W. J. M.]
Eleven dogs with spontaneous neoplasms were intensively treated with an immunoadsorption system consisting of a continuous flow centrifuge, Protein A-Sepharose columns, and a semi-automatic elution system. Despite consistent and substantial lowering of immunoglobulin G levels, tumor regression was noted in only one of 11 dogs.
In contrast, infusion of small volumes of plasma after incubation with heat and formalin-treated Staphylococcus aureus Cowan I resulted in a tumoricidal response in five of six animals. These results suggest that tumor necrosis is probably not induced by Protein A-mediated removal of humoral "blocking" factors." (emphasis added here)."To download the full text of the article, please
CLICK HERE (The article is around 3.5 megabytes).
But, here is
ANOTHER article which is equally important on this topic.
"
EXTRACORPOREAL PERFUSION OF PLASMA OVER IMMOBILIZED STAPHYLOCOCCUS AUREUS PROTEIN A AS A TREATMENT FOR FELV INFECTION AND LYMPHOSARCOMA: PROSPECTS FOR TREATMENT OF RETROVIRAL INFECTION AND AIDS IN MAN
Animal Models of Retrovirus Infection and Their Relationship to AIDS.
Salzman LA, ed. Orlando, Florida, Academic Press, p. 403-19, 1986.. Unique
Identifier : AIDSLINE ICDB/87629290
Snyder HW Jr; Singhal MC; Ernst NR; Grant CK; Cotter SM;
Yoshida LH; Jones FR; Immune Response Program, Pacific Northwest Res.
Foundation,; Seattle, WA
Abstract:
The feline leukemia virus (FeLV) is a contagious T cell lymphotropic retrovirus that productively infects lymphoid and myeloid cells in approx 30% of exposed pet cats. After the onset of viremia, death usually results within 3 mo to 3 yr due to degenerative bone marrow disease, leukemia, lymphosarcoma (LSA), or, more likely, opportunistic infections secondary to an FeLV-acquired immune deficiency syndrome (FAIDS). There are numerous similarities between FAIDS and human acquired immune deficiency syndrome (AIDS). Both syndromes are characterized by lymphopenia, reduced lymphocyte response to mitogens and allogeneic cells, cutaneous anergy, impaired antibody responses, and secondary infections; furthermore, AIDS like FAIDS, also appears to be caused by a retrovirus, which is termed human T cell lymphotropic virus type III (HTLV-III), lymphadenopathy-associated virus (LAV), or AIDS-related retrovirus (ARV). In the authors' laboratories, the biochemistry and immunology of FeLV and FeLV-induced LSA have been studied and, recently, the value of viral cell surface antigens as targets for immunotherapy has been assessed. Results of these studies and their potential applications for the treatment of AIDS are discussed under the following section headings: FeLV proteins which function as cellular antigens; immunological intervention in feline retrovirus infections; treatment of feline LSA and persistent FeLV infection by extracorporeal immunoadsorption of plasma over Staphylococcus aureus Cowan I (SAC); antibody responses against LSA and FeLV in cats treated by extracorporeal immunoadsorption of plasma over SAC; treatment of feline LSA, leukemia, and persistent FeLV infection using purified SAC-derived protein A (SpA); and application of extracorporeal immunoadsorption of plasma over SpA columns as a treatment for Kaposi's sarcoma associated with AIDS. The rationale for the application of the extracorporeal immunoabsorption therapy is explained in detail. The responses of FeLV clearance and tumor regression achieved in cats with FAIDS and persistent FeLV infection using extracorporeal immunoadsorption therapy suggest that it may have application in the treatment of human AIDS and persistent HTLV-III/LAV/ARC infection. (46 Refs)."
Here is another
article abstract
"
Immunomodulation therapy for feline leukemia virus infection
Clinically ill feline leukemia virus (FeLV)-infected cats, treated with
Staphylococcus protein A (SPA) or oral interferon alpha (IFN), or both, were
compared with cats treated with saline (SAL). Nine cats received SPA/SAL, nine
received SPA/IFN, 10 received SAL/IFN, and eight received SAL/SAL. Twelve cats
survived and completed the 100-week therapy. Significantly more owners of cats
treated with SPA/SAL thought their cat's health improved during treatment
compared to owners of cats treated with SAL/SAL (P=0.05, pair-wise comparison)
or SPA/IFN (P=0.05, pair-wise comparison). No significant differences in body
weight, temperature, hematocrit, red blood cell counts, mean corpuscular
hemoglobin concentration, reticulocyte counts, white blood cell or neutrophil
numbers, lymphocyte concentrations, bone-marrow cytopathology, FeLV status,
survival time, activity, or appetite scores were observed. No significant
differences in the owners' subjective assessment of their cat's health following
treatment with SAL/IFN, SPA/IFN, or SAL/SAL were seen. Therapy with SPA as a
single agent results in the owners' subjective impression of improved health of
their FeLV-infected cats. "
And, another article (click to download the PDF version)
"
Treatment of plasma or serum from leukemic patients with solid phase Staphylococcal Protein A induced leukemic blast cell lysis in vitro, but this effect was relatively independent of the amount of immunoglobulinG (IgG) removed. Samples with approximately equal cytotoxic activity contained markedly different IgG levels, while samples with similar IgG levels had a wide range of tumoricidal activity. Assays of plasma samples collected during a perfusion of one plasma volume through a Protein ASepharose column indicated that the duration of the procedure had a greater effect on cytotoxic activity than did the amount of IgG removed. Neither added leukemic nor normal IgG significantly improved blast cell viability in treated serum. Cytotoxic activity was not dialyzable and concentrated in the M, < 100,000 fraction of samples separated by nitration. Treated cytotoxic serum samples did not have important Clq binding activity. These results suggest that the in vitro tumoricidal activity of solid phase Protein A is probably due to a toxic substance added to serum during immunoadsorption rather than to its immunoadsorptive capacity. "
In the DISCUSSION, the authors come up with their own
conclusions about the importance
of SAC (Staph Protein A Cowan I) and its ability to bind CIC (circulating immune
complexes)
and IGg (immunglobulin G) as an active mechanism of tumor fighting.
" DISCUSSION
The use of Protein A-containing immunoadsorption systems in cancer patients developed from the idea that this bacterial cell wall component might remove circulating blocking factors more specifically than plasma exchange (1). When the predicted tumor necrosis was observed, it was logical to assume that reduction of IgG and/or IgG containing immune complexes was at least partly responsible for the clinical effect. However, subsequent observations have cast doubt upon this interpretation. For example, clinical responses were often noted after treatment of small volumes of plasma with relatively little Protein A, limiting the possible impact on total body levels of immunoglobulin (6). Similarly, infusion of small volumes of SAC-treated plasma resulted in frequent clinical responses, while intensive removal of IgG with Protein A-Sepharose columns was less effective (5). When measured, immune complex levels were usually relatively unaffected or, in fact, increased by Protein A perfusion (2, 5, 23. 24). Finally, some, but not all, laboratories have reported tumor regressions following exposure of plasma to staphylococcal strains, such as Wood 46, which lack Protein A (11).
The studies reported here provide further evidence that removal of IgG and immune complexes has little to do with the antitumor activity of Protein A. Using an in vitro system, we onfirmed our earlier observation that exposure of patient plasma to SAC or Protein A-Sepharose regularly (but not invariably) reduces leukemic blast cell viability. However, this effect did not correlate with the extent of removal of IgG or immune complexes (as measured by Clq binding activity).
Moreover, addition of leukemic or normal IgG to SAC-treated serum did not significantly alter blast viability. We interpret these findings to mean that, at least in our experimental system, the tumoricidal effect of solid phase Protein A is relatively independent of its immunoadsorptive properties.
This conclusion is of some practical importance, in that
large absorptive capacity may not be a necessary feature of systems designed to
use solid phase Protein A as a treatment modality.In fact, the opposite may be
the case. We found that plasma samples obtained late in perfusion treatments,
when the Protein A-Sepharose was nearly saturated, produced more cytotoxicity
than did samples collected early in the perfusion when IgG removal was extensive
(Fig. 2). To the extent that this model system reflects the ex vivo situation,
this evidence suggests that the duration of plasma exposure to solid phase
Protein A may be important, and that smaller quantities of Protein A may be as
effective as are the costly large perfusion columns. The studies presented here
indicate that the mechanism of Protein A tumoricidal activity involves more than
simple immunoglobulin removal. Our previous in vitro studies showed that
SAC-treated leukemic sera were more cytotoxic for leukemic cells than were
SAC-treated normal sera (17), and we have not ruled out participation of
leukemic serum factors in this cytotoxicity. Our present
studies suggest, however, that release of Protein A or other bacterial products,
such as enterotoxin A, which has been reported to contaminate commercial Protein
A (25), may be involved in the Protein A-induced tumorcidal activity." (
I changed the color of the last
sentence to add emphasis on their conclusion).
HOW DOES THIS RELATE TO THE IMMUNOPATHOLOGY INDUCED BY THE FELINE LEUKEMIA VIRUS
?
See this excerpt of the William Hardy , Jr. Article below
http://www.springerlink.com/content/p2731678783g06t6/fulltext.pdf?page=1
" Introduction
The observation by Old and his coworkers in 1960 that infection of mice with
Friend leukemia virus interfered with the production of antibodies against sheep red
blood cells stimulated investigations into the effects of oncogenic viruses on the
immune system [96]. There have been numerous reports of immunosuppression in
birds and mammals induced by infection with oncogenic viruses (Table 1) 1-21,943,
and it has been postulated that the impairment of the normal immune function is
necessary for the survival and proliferation of tumor cells [13, 373. In some studies it
has been found that AKR mice have lower numbers of circulating lymphocytes, a
decreased spleen weight, and decreased bone marrow cellularity, suggesting that
their cellular immune system has been depleted [1133.
The feline leukemia virus (FeLV) replicates in rapidly dividing cells, such as
lymphocytes, granulocytic leukocytes, and erythroid progenitor cells, and causes
neoplastic diseases of these cells, or more commonly causes degenerative blastopenic
diseases by damaging these cells in some way (Table 2) [42, 43, 45, 46, 83]. For
example, lymphosarcoma is a proliferative disease of lymphocytes (usually thymic
lymphocytes) whereas thymic atrophy is a degenerative disease
of thymic lym-"
( You have to purchase the article to read the rest )
PLACES TO GET STAPH PROTEIN A and the PROTOCOL
Staph Protein A
1) Amersham Pharmacia Biotech 800 526 3593
2) Sigma Chemical Company 800 325 3010
3) Pierce Chemical 800 874 3723
4) ProZyme 800 457 9444
PROTOCOL: 20ug/2.75 kg given IP twice weekly or 500 to 5000ug/cat (ave. 2000 ug)
twice weekly
-----------------------------------------------------
OTHER RELATED SITES AND LINKS
http://www.dumplinbaker.com
http://dumplinbaker.angelfire.com
http://dumplin.terapad.com
http://cats.terapad.com
http://dumplinbaker.blogspot.com
Keywords= taph protein A, staphylococcus aureus, cowan I,
FeLV, feline leukemia, remission, treatment,
IGg, IgG, cic, circulating immune complexes, leukemia, cancer, neoplasms,
lymphosarcoma, LSA, immunomodulation