The Presence of Complement in Human Cervical Mucus and its Possible Relevance to Infertility in Women with Complement-Dependent Sperm-Immobilizing Antibodies

Price, Rhelma J.; Boettcher, B.

doi:10.1016/s0015-0282(16)44117-8

Cited by 130 publications

(78 citation statements)

References 6 publications

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“…Full AP complement activity is reported in cervical mucous (Price and Boettcher, 1979;Vanderpuye et al, 1992); however, C4 of the complement classical pathway (CP) is only detected in a small subpopulation of luteal-phase cervical secretions (Vanderpuye et al, 1992). Collectively, these data suggest that the presence of CR3 within the female genital tract might function to eliminate exogenous antigens, after their inactivation in seminal fluid or cervical mucous, without a neutrophil influx.…”

Section: Discussionmentioning

confidence: 96%

The role of complement receptor 3 (CR3) inNeisseria gonorrhoeaeinfection of human cervical epithelia

Edwards¹,

Brown²,

Ault³

et al. 2001

Cellular Microbiology

115

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Section: Discussionmentioning

confidence: 96%

The role of complement receptor 3 (CR3) inNeisseria gonorrhoeaeinfection of human cervical epithelia

Edwards¹,

Brown²,

Ault³

et al. 2001

Cellular Microbiology

115

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“…It has also been demonstrated in vitro that Ab neutralization of CD59 rendered human sperm susceptible to MAC-induced damage, as indicated by increased immobility and membrane permeability (39). Since functional complement components are abundant in the female reproductive tract (41,42), it has been speculated that CD59 may be involved in protecting the sperm from complement-mediated damage that might be initiated by anti-sperm Abs present in the female reproductive tract (38 -40). With the identification of cd59b, this hypothesis, as well as the precise pattern of CD59 distribution within the testis and the possible roles of CD59 in other aspects of testicular function can be addressed using the mouse as an animal model.…”

Section: Discussionmentioning

confidence: 99%

Identification and Functional Characterization of a New Gene Encoding the Mouse Terminal Complement Inhibitor CD59

Qian

Qin

Miwa

et al. 2000

The Journal of Immunology

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CD59 is a 18- to 20-kDa, GPI-anchored membrane protein that functions as a key regulator of the terminal step of the complement activation cascade. It restricts binding of C9 to the C5b-8 complex, thereby preventing the formation of the membrane attack complex (C5b-9 of complement). A single human CD59 gene has been identified, and corresponding genetic homologues from rat, mouse, and pig have been characterized in previous studies. In this study, we report the discovery and functional characterization of a separate cd59 gene in the mouse (referred to as cd59b, the previously characterized mouse cd59 gene as cd59a). Mouse cd59b is 85% and 63% identical to cd59a at the nucleotide and amino acid level, respectively. In cDNA transfection experiments with Chinese hamster ovary cells, peptide-tagged cd59b was detected on the cell surface by flow cytometry and was shown to be susceptible to phosphatidylinositol-specific phospholipase C cleavage. Chinese hamster ovary cells expressing cd59b were significantly more resistant than control cells to human and mouse complement-mediated lysis. These results suggest that cd59b encodes a GPI-anchored protein that is functionally active as a membrane attack complex inhibitor. Northern blot analysis revealed that cd59b is expressed selectively in the mouse testis. In contrast, the major transcript of cd59a was shown to be expressed at high levels in the heart, kidney, liver, and lung, but only minimally in the testis. These results revealed the existence of two distinct cd59 genes in the mouse that are differentially regulated and that may have nonoverlapping physiological functions in vivo.

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“…The concentration of human fH (HufH) in plasma is ϳ500 g/ml. All of the complement proteins that are necessary to exhibit full complement-related lytic (or direct bactericidal) activity are present in cervical mucus at levels that approximate 10% of that seen in undiluted human serum (19).…”

mentioning

confidence: 99%

Human Factor H Interacts Selectively with Neisseria gonorrhoeae and Results in Species-Specific Complement Evasion

Ngampasutadol

Ram

Gulati

et al. 2008

The Journal of Immunology

116

143

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Complement forms a key arm of innate immune defenses against gonococcal infection. Sialylation of gonococcal lipo-oligosaccharide, or expression of porin 1A (Por1A) protein, enables Neisseria gonorrhoeae to bind the alternative pathway complement inhibitor, factor H (fH), and evade killing by human complement. Using recombinant fH fragment-murine Fc fusion proteins, we localized two N. gonorrhoeae Por1A-binding regions in fH: one in complement control protein domain 6, the other in complement control proteins 18–20. The latter is similar to that reported previously for sialylated Por1B gonococci. Upon incubation with human serum, Por1A and sialylated Por1B strains bound full-length human fH (HufH) and fH-related protein 1. In addition, Por1A strains bound fH-like protein 1 weakly. Only HufH, but not fH from other primates, bound directly to gonococci. Consistent with direct HufH binding, unsialylated Por1A gonococci resisted killing only by human complement, but not complement from other primates, rodents or lagomorphs; adding HufH to these heterologous sera restored serum resistance. Lipo-oligosaccharide sialylation of N. gonorrhoeae resulted in classical pathway regulation as evidenced by decreased C4 binding in human, chimpanzee, and rhesus serum but was accompanied by serum resistance only in human and chimpanzee serum. Direct-binding specificity of HufH only to gonococci that prevents serum killing is restricted to humans and may in part explain species-specific restriction of natural gonococcal infection. Our findings may help to improve animal models for gonorrhea while also having implications in the choice of complement sources to evaluate neisserial vaccine candidates.

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The Presence of Complement in Human Cervical Mucus and its Possible Relevance to Infertility in Women with Complement-Dependent Sperm-Immobilizing Antibodies

Cited by 130 publications

References 6 publications

The role of complement receptor 3 (CR3) inNeisseria gonorrhoeaeinfection of human cervical epithelia

The role of complement receptor 3 (CR3) inNeisseria gonorrhoeaeinfection of human cervical epithelia

Identification and Functional Characterization of a New Gene Encoding the Mouse Terminal Complement Inhibitor CD59

Human Factor H Interacts Selectively with Neisseria gonorrhoeae and Results in Species-Specific Complement Evasion

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