Identification of C1q as the heat-labile serum cofactor required for immune complexes to stimulate endothelial expression of the adhesion molecules E-selectin and intercellular and vascular cell adhesion molecules 1

Carlos Lozada, Richard I. Levin, Maryann Huie, Rochelle Hirschhorn, Dwight Naime, Michael Whitlow, Phoebe A. Recht, Brian Golden, Bruce N. Cronstein

Research output: Contribution to journalArticle

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Abstract

To examine the role of complement components as regulators of the expression of endothelial adhesive molecules in response to immune complexes (ICs), we determined whether ICs stimulate both endothelial adhesiveness for leukocytes and expression of E-selectin and intercellular and vascular cell adhesion molecules 1 (ICAM-1 and VCAM-1). We found that ICs [bovine serum albumin (BSA)-anti-BSA] stimulated endothelial cell adhesiveness for added leukocytes in the presence of complement-sufficient normal human serum (NHS) but not in the presence of heatinactivated serum (HIS) or in tissue culture medium alone. Depletion of complement component C3 or C8 from serum did not prevent enhanced endothelial adhesiveness stimulated by ICs. In contrast, depletion of complement component C1q markedly inhibited IC-stimulated endothelial adhesiveness for leukocytes. When the heat-labile complement component C1q was added to HIS, the capacity of ICs to stimulate endothelial adhesiveness for leukocytes was completely restored. Further evidence for the possible role of C1q in mediating the effect of ICs on endothelial cells was the discovery of the presence of the 100- to 126-kDa C1q-binding protein on the surface of endothelial cells (by cytofluorography) and of message for the 33-kDa C1q receptor in resting endothelial cells (by reverse transcription-PCR). Inhibition of protein synthesis by cycloheximide blocked endothelial adhesiveness for leukocytes stimulated by either interleukin 1 or ICs in the presence of NHS. After stimulation with ICs in the presence of NHS, endothelial cells expressed increased numbers of adhesion molecules (E-selectin, ICAM-1, and VCAM-1). Endothelial expression of adhesion molecules mediated, at least in part, endothelial adhesiveness for leukocytes, since leukocyte adhesion was blocked by monoclonal antibodies directed against E-selectin. These studies show that ICs stimulate endothelial cells to express adhesive proteins for leukocytes in the presence of a heat-labile serum factor. That factor appears to be C1q.

Original languageEnglish
Pages (from-to)8378-8382
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number18
StatePublished - Aug 29 1995
Externally publishedYes

Fingerprint

E-Selectin
Vascular Cell Adhesion Molecule-1
Antigen-Antibody Complex
Adhesiveness
Hot Temperature
Leukocytes
Serum
Endothelial Cells
Complement C1q
Intercellular Adhesion Molecule-1
Bovine Serum Albumin
Adhesives
Complement C8
Complement C3
Cycloheximide
Interleukin-1
Reverse Transcription
Culture Media
Proteins
Monoclonal Antibodies

Keywords

  • Endothelium
  • Immune complex
  • Leukocyte
  • Vasculitis

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Identification of C1q as the heat-labile serum cofactor required for immune complexes to stimulate endothelial expression of the adhesion molecules E-selectin and intercellular and vascular cell adhesion molecules 1. / Lozada, Carlos; Levin, Richard I.; Huie, Maryann; Hirschhorn, Rochelle; Naime, Dwight; Whitlow, Michael; Recht, Phoebe A.; Golden, Brian; Cronstein, Bruce N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 18, 29.08.1995, p. 8378-8382.

Research output: Contribution to journalArticle

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abstract = "To examine the role of complement components as regulators of the expression of endothelial adhesive molecules in response to immune complexes (ICs), we determined whether ICs stimulate both endothelial adhesiveness for leukocytes and expression of E-selectin and intercellular and vascular cell adhesion molecules 1 (ICAM-1 and VCAM-1). We found that ICs [bovine serum albumin (BSA)-anti-BSA] stimulated endothelial cell adhesiveness for added leukocytes in the presence of complement-sufficient normal human serum (NHS) but not in the presence of heatinactivated serum (HIS) or in tissue culture medium alone. Depletion of complement component C3 or C8 from serum did not prevent enhanced endothelial adhesiveness stimulated by ICs. In contrast, depletion of complement component C1q markedly inhibited IC-stimulated endothelial adhesiveness for leukocytes. When the heat-labile complement component C1q was added to HIS, the capacity of ICs to stimulate endothelial adhesiveness for leukocytes was completely restored. Further evidence for the possible role of C1q in mediating the effect of ICs on endothelial cells was the discovery of the presence of the 100- to 126-kDa C1q-binding protein on the surface of endothelial cells (by cytofluorography) and of message for the 33-kDa C1q receptor in resting endothelial cells (by reverse transcription-PCR). Inhibition of protein synthesis by cycloheximide blocked endothelial adhesiveness for leukocytes stimulated by either interleukin 1 or ICs in the presence of NHS. After stimulation with ICs in the presence of NHS, endothelial cells expressed increased numbers of adhesion molecules (E-selectin, ICAM-1, and VCAM-1). Endothelial expression of adhesion molecules mediated, at least in part, endothelial adhesiveness for leukocytes, since leukocyte adhesion was blocked by monoclonal antibodies directed against E-selectin. These studies show that ICs stimulate endothelial cells to express adhesive proteins for leukocytes in the presence of a heat-labile serum factor. That factor appears to be C1q.",
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AU - Huie, Maryann

AU - Hirschhorn, Rochelle

AU - Naime, Dwight

AU - Whitlow, Michael

AU - Recht, Phoebe A.

AU - Golden, Brian

AU - Cronstein, Bruce N.

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