Engagement of the monocyte surface antigen CD14 induces lymphocyte function-associated antigen-1/intercellular adhesion molecule-1-dependent homotypic adhesion.
Murine anti-CD14 mAb which recognize different CD14 epitopes induced marked homotypic adhesion of normal human monocytes. Induction of aggregation by anti-CD14 mAb required Mg2+, occurred at an optimal temperature of 37 degrees C, but not at 4 degrees C, and exhibited a kinetics which differed from adhesion triggered by IFN-gamma and anti-CD43 mAb. Monocyte adhesion induced by anti-CD14 mAb required neither Fcy gamma R engagement nor cross-linking of CD14, because adhesion was induced by F(ab)'2 fragments, as well as by monovalent F(ab) fragments of anti-CD14 mAb. mAb to CD11a, CD18, and intercellular adhesion molecule-1 (ICAM-1), but not antibodies to CD11b and CD11c, inhibited monocyte adhesion induced by CD14 engagement. These results indicate that CD14-dependent adhesion is mediated by lymphocyte function-associated Ag-1/ICAM-1 interactions. This was confirmed by the absence of aggregation in anti-CD14-stimulated cells from a patient with leukocyte adhesion deficiency. Monocyte adhesion upon CD14 engagement was blocked by an inhibitor of protein kinases, sphingosine. This suggests that protein kinases play a role in the intracellular signaling pathway(s) which couple CD14 to lymphocyte function-associated Ag-1/ICAM-1.
Lauener
R P
RP
Division of Immunology, Children's Hospital, Boston, MA 02115.
Geha
R S
RS
Vercelli
D
D
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D018950:Lipopolysaccharide Receptors; D016169:Lymphocyte Function-Associated Antigen-1; D008274:Magnesium / Q000502:physiology; D009000:Monocytes / Q000166:cytology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D011940:Receptor Aggregation; D011961:Receptors, Fc / Q000502:physiology; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D015398:Signal Transduction; D013110:Sphingosine / Q000494:pharmacology; D013696:Temperature
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D018950:Lipopolysaccharide Receptors; D016169:Lymphocyte Function-Associated Antigen-1; D047428:Protein Kinase Inhibitors; D011961:Receptors, Fc; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1; D011494:Protein Kinases; D008274:Magnesium; D013110:Sphingosine