The role of immunoglobulin binding factors in the pathogenesis and therapy of AIDS

Cowan, Fred M.; Madsen, Jill

doi:10.1016/0306-9877(94)90148-1

Cited by 5 publications

(5 citation statements)

References 33 publications

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“…Such phagocytosis usually results in digestion of the particles; however, HIV is one of several pathogens which can escape such digestion and establish a productive infection within the cells [4], and this process is facilitated by opsonization of the virus with immunoglobulin and/or complement [5]. It is reported that neutralizing antibodies to HIV develop following infections [6], but several studies have characterized mechanisms of antibody enhancement of HIV infection [7][8][9] and antibody-dependent complementmediated enhancement [8,10]. This facilitation of HIV infection is dependent on the expression FcgRI and CR1 receptors.…”

Section: Introductionmentioning

confidence: 99%

Progression of HIV disease is associated with increased expression of FcγRI and CR1 on alveolar macrophages

Gilbody

Lipman

Johnson

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe expression of receptors for complement and the Fc region of immunoglobulin by alveolar macrophages (AM) constitutes a valuable aid to effector function of these cells. However, during HIV infection such expression may also act to increase binding of immune complexes, thus facilitating viral infection of these cells. This study was designed to determine whether changes in the expression of these receptors occurs in situ during HIV infection. Lung macrophages were isolated by bronchoalveolar lavage in groups of HIV + subjects segregated on the basis of peripheral CD4 count. A group of normal subjects was also investigated. Expression of CR1 and FcgRI was quantified by measuring the optical density of reaction product following controlled immunoperoxidase staining with MoAbs CD35 and CD64. Both CR1 and FcgRI were increased over normal in all HIV + subjects. This increase was progressive with advancing disease as determined by correlation with declining peripheral CD4 count. Comparison of asymptomatic and symptomatic subjects with HIV infection showed no difference in CR1 expression but a rise in FcgRI expression in the latter group. An overall inverse correlation was also found between peripheral CD4 count and FcgRI expression, but not CR1 expression. These data demonstrate a significant increase in the expression of these receptors on AM from HIV + subjects, and show that this increase may occur before any symptoms in these patients.

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Section: Introductionmentioning

confidence: 99%

Progression of HIV disease is associated with increased expression of FcγRI and CR1 on alveolar macrophages

Gilbody

Lipman

Johnson

et al. 1997

Clinical and Experimental Immunology

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“…The IBF activ ity of SPA may affect FcR im m unity that encom passes effector functio ns, such as antibo dy dependent cellu lar cytoto xicity (A DCC), phagocytosis and complem ent activation, and regulato ry signals for B and T cells [9±15]. The paradox that S PA can both augm ent or inhibit im m unity is re¯ected in the ef® cacy of S PA im munotherapy to stim ulate im munity to cancer and viral antig ens and to inhibit autoim m unity (rev iew ed in [14,15]). The activ ation and suppressio n of im munity by the bacterial IB F SPA is possib le a result of changing the concentratio n of IB F relativ e to other serum factors, e.g., antib odies and im m une com plexes, subsequently modulatin g the interactio n of serum facto rs with im mune effecto r and regulato ry, e.g., T helper and suppresso r cells (rev iew ed in [14,15]) ( Figure 1).…”

mentioning

confidence: 99%

“…The ® rst attem pt to construct an im munoadhesin was attrib uted to Gascoig ne et al (reviewed in [17]). However, the use of im m une receptors such as FcR or``cou nterfeit' ' micro bial products that im itate these recep tors, such as SPA, now constitu tes a m ajor thru st for drug develo pment in im m unopharm acolo gy, with publication s by Cowan et al (rev iew ed in [15]) and patent by Cowan [14] datin g back to 1979.…”

mentioning

confidence: 99%

“…The HIV envelope protein s gp120 and gp41, lik e S PA, have FcR-lik e activ ity and like SP A, HIV gp120 PROTEIN A IM M UNOTHERAPY also binds to IgM Fab VH3, actin g as a B cell``su per antigen [15,36]. The expressio n of F c and Fab antib ody binding by both a bacteria l and a viral protein , in lig ht of the lim ited amount of genetic material available to code for viral protein function , indicates that coexpression of these recep tors m ay involve possib ly synergistic im m unomodulating action (s).…”

mentioning

confidence: 99%

“…Such crosslinking of B cell IgM and FcR by im m une com plexes m ight be augm ented by the Fc and F ab binding activities of S PA or HIV gp120 and contrib ute to down regulation or clonal deletion of activated lym phocytes. This might explain som e of the abnorm al B cell response associated with HIV infection [15], and the long-term rem issio ns of autoimm une disease associated with SPA im m unotherap y [6]. S PA with F c and Fab activ ities and S PA that has been altered to express only FcR or Fab activ ity [40] could be used in B cell in vitro m odels to test this hypothesis.…”

mentioning

confidence: 99%

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Staphylococcus Aureus Protein A Immunoadsorption: The Rationale for Systemic Protein A Immunotherapy

Cowan

1997

Toxicology Methods

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Sum m ary:Staphylo coccus aureus protein A (SPA) bound to af® nity colum n m atrixes has been used for extracorp oreal imm unoadsorp tion for the treatm ent of hum an autoim m une and neoplastic diseases. SPA is a bacterial im munoglobu lin binding factor (IBF) that binds to the Fc region of antibody. T he mechanism (s) of action of protein A im munoadsor ption is not know n. However, protein A im munoadsorpt ion and system ic injection of SPA have dem onstrated sim ilar anti-neo6 -plastic and anti-retro viral responses in anim als. Cellular Fc receptor (FcR) im munity and hum oral IBF status are often abnorm al in autoim munity, cancer, and AIDS. T he im munothera peutic activity of protein A im munoadsor ption m ay be produced by SPA leaching off colum ns and acting as a soluble FcR-like IBF, capable of in¯uencing FcR dependent im munity. If this is the case then system ic SPA therapy may provide a sim pler, safer, and more predicabl e mode of immunotherapy than imm unoadsorp tion. K ey W ord s: extracorp oreal, Fc receptor, imm unoglobuli n binding factor, Staphyloc occus aureus protein A.Extraco rporeal im m unotherapy with protein A containin g bacteria was ® rst used by Bansal et al. in 1978 [1] to treat canin e and human breast adenocarcinom a. Since that tim e S ynder et al. [2], Term an et al. [3], M esserschm idt et al. [4], Kinet [5], and others [6] have continu ed investigati on of the anti-neo plastic activ ity of protein A im m unoadsorption . Despite the prelim inary clinica l success for treatin g som e autoimm une and neoplastic diseases [6] such as breast adenocarcin om a, Kaposi' s sarco m a, and refractory rheumatoid arth ritis [7], S PA colum n treatm ent of autoim m une thrombocytopenic purpura (IT PP) is the only use approved by United States Food and Drug Adm inistrat ion [6,8]. Num erous clin ical param eters such as circulating im m une

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Enhanced Proteolytic Activity and Fc Receptor Expression in Human Epithelial Cells Following Exposure to Sulfur Mustard

Cowan¹,

Broomfield²,

Smith³

1999

Toxicity Assessment Alternatives

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The role of immunoglobulin binding factors in the pathogenesis and therapy of AIDS

Cited by 5 publications

References 33 publications

Progression of HIV disease is associated with increased expression of FcγRI and CR1 on alveolar macrophages

Progression of HIV disease is associated with increased expression of FcγRI and CR1 on alveolar macrophages

Staphylococcus Aureus Protein A Immunoadsorption: The Rationale for Systemic Protein A Immunotherapy

Enhanced Proteolytic Activity and Fc Receptor Expression in Human Epithelial Cells Following Exposure to Sulfur Mustard

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