Identification of human complement factor H as a chemotactic protein for monocytes

Nabil, Karim Mahmoud; Rihn, Bertrand; Jaurand, Marie‐Claude; Vignaud, Jean-Michel; Ripoche, Jean; Martinet, Yves; Martinet, Nadine

doi:10.1042/bj3260377

Cited by 45 publications

(35 citation statements)

References 31 publications

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“…Several studies indicate the existence of specific CFH receptors on human cells, although the data are inconclusive (47)(48)(49)(50)(51). No receptor, except for CR3 on neutrophils, was identified at the molecular level.…”

Section: Discussionmentioning

confidence: 99%

Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida albicans, and Enhance Neutrophil Antimicrobial Activity

Losse¹,

Zipfel

Józsi³

2009

The Journal of Immunology

100

124

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The host complement system plays an important role in protection against infections. Several human-pathogenic microbes were shown to acquire host complement regulators, such as factor H (CFH), that downregulate complement activation at the microbial surface and protect the pathogens from the opsonic and lytic effects of complement. Because CFH can also bind to host cells, we addressed the role of CFH and CFH-related proteins as adhesion ligands in host-pathogen interactions. We show that the CFH family proteins CFH, CFH-like protein 1 (CFHL1), CFH-related protein (CFHR) 1, and CFHR4 long isoform bind to human neutrophil granulocytes and to the opportunistic human-pathogenic yeast Candida albicans. Two major binding sites, one within the N-terminus and one in the C-terminus of CFH, were found to mediate binding to neutrophils. Complement receptor 3 (CD11b/CD18; αMβ2 integrin) was identified as the major cellular receptor on neutrophils for CFH, CFHL1, and CFHR1, but not for CFHR4 long isoform. CFH and CFHR1 supported cell migration. Furthermore, CFH, CFHL1, and CFHR1 increased attachment of neutrophils to C. albicans. Adhesion of neutrophils to plasma-opsonized yeasts was reduced when CFH binding was inhibited by specific Abs or when using CFH-depleted plasma. Yeast-bound CFH and CFHR1 enhanced the generation of reactive oxygen species and the release of the antimicrobial protein lactoferrin by human neutrophils, and resulted in a more efficient killing of the pathogen. Thus, CFH and CFHR1, when bound on the surface of C. albicans, enhance antimicrobial activity of human neutrophils.

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Section: Discussionmentioning

confidence: 99%

Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida albicans, and Enhance Neutrophil Antimicrobial Activity

Losse¹,

Zipfel

Józsi³

2009

The Journal of Immunology

100

124

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“…Like CR1, factor H is a versatile protein with several different functions. It inhibits the formation and accelerates the decay of C3 convertases, serves as a cofactor for factor I (45), displays chemotactic activity for monocytes (46), and possibly participates in interactions with extracellular matrix and leukocytes (47).…”

Section: Fig 5 Flow Cytometric Analysis Of Factor H On Rat Plateletsmentioning

confidence: 99%

A Protein with Characteristics of Factor H Is Present on Rodent Platelets and Functions as the Immune Adherence Receptor

Alexander

Hack

Cunningham

et al. 2001

Journal of Biological Chemistry

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Complement-coated particles interact with specific immune adherence receptors (IAR). In primates, this function is served by complement receptor 1 (CR1) on erythrocytes. In contrast, rodent platelets bear IAR distinct from CR1, the identity of which was studied here. A 150-kDa C3b-binding protein was isolated from rat platelets, which had immunochemical and biochemical identity to plasma factor H. Immunofluorescence microscopy and flow cytometry demonstrated that factor H was present on the surface of rat and mouse platelets, which could be removed by treatment with neuraminidase. Sheep erythrocytes bearing C3b underwent immune adherence with rat and mouse platelets, which was blocked with anti-factor H F(ab) 2 antibodies, but not with antibodies binding to the complement regulator, Crry, on the platelet surface. By reverse transcription-polymerase chain reaction using rat platelet RNA and primers designed from mouse factor H, a 472-base pair product was generated that was identical in sequence to that produced from rat liver RNA. The translated protein product was 85% similar to mouse liver factor H. The 3-nucleotide sequence from platelets predicted a soluble factor H protein. By Northern analysis, liver and platelets had identically sized factor H mRNA. Thus, rat and mouse platelets have a membrane protein with characteristics of factor H that is linked via sialic acid residues and functions as the IAR. Whether platelet factor H is acquired by passive adsorption from sera and/or is produced by platelets remains to be determined.

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“…In addition to its regulation of complement activation, other functions have been found for factor H. It is a ligand for L-selectin (15) and also binds to the integrin Mac-1 (CD11b/CD18), enhancing the activation response of human neutrophils (16). Factor H also induces the secretion of interleukin 1␤ by monocytes (17) and acts as a chemotactic protein for these cells (18). Factor H binds to cell surface components of several pathogens (19 -23), inhibiting the alternative pathway of complement and thus enhancing their pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

Expression of Complement Factor H by Lung Cancer Cells

et al. 2004

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The complement system is important in immunosurveillance against tumors. However, malignant cells are usually resistant to complementmediated lysis. In this study, we examine the expression of factor H, an inhibitor of complement activation, and factor H-like protein 1 (FHL-1), its alternatively spliced form, in lung cancer. We also evaluate the potential effect of factor H/FHL-1 in the protection of lung cancer cells against the activation of the complement cascade. By Northern blot analysis we demonstrate a high expression of factor H and FHL-1 in most non-small cell lung cancer cell lines, although neuroendocrine pulmonary tumors (small cell lung carcinoma and carcinoid cell lines) had undetectable levels. Western blot analysis of conditioned medium showed the active secretion of factor H and FHL-1 by cells that were positive by Northern blot. Expression of factor H/FHL-1 mRNA was also shown in a series of non-small cell lung cancer biopsies by in situ hybridization. Interestingly, many cultured lung cancer cells were able to bind fluorescence-labeled factor H to their surfaces. Deposition of C3 fragments from normal human serum on H1264, a lung adenocarcinoma cell line, was more efficient when factor H/FHL-1 activity was blocked by specific antibodies. Blocking factor H/FHL-1 activity also enhanced the release of anaphylatoxin C5a and moderately increased the susceptibility of these cells to complement-mediated cytotoxicity. In summary, we demonstrate the expression of factor H and FHL-1 by some lung cancer cells and analyze the contribution of these proteins to the protection against complement activation.

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Identification of human complement factor H as a chemotactic protein for monocytes

Cited by 45 publications

References 31 publications

Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida albicans, and Enhance Neutrophil Antimicrobial Activity

Factor H and Factor H-Related Protein 1 Bind to Human Neutrophils via Complement Receptor 3, Mediate Attachment to Candida albicans, and Enhance Neutrophil Antimicrobial Activity

A Protein with Characteristics of Factor H Is Present on Rodent Platelets and Functions as the Immune Adherence Receptor

Expression of Complement Factor H by Lung Cancer Cells

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