A form of circulating ICAM-1 in human serum.
A circulating form of the usually membrane-bound intercellular adhesion molecule-1 (ICAM-1) was identified and characterized in normal human serum, and in sera from patients with leukocyte adhesion deficiency (LAD). The molecule, designated circulating ICAM-1 (cICAM-1) was detected and quantitated by sandwich ELISA. Levels of cICAM-1 in sera from normal individuals ranged from 100 to 200 ng/ml. Sera from LAD patients had elevated cICAM-1 levels ranging from 200 to 700 ng/ml. The elevated levels of cICAM-1 in LAD sera may be due to an inability to adsorb cICAM-1 to cell-bound LFA-1 or may be an indirect result of the pathology accompanying the syndrome. cICAM-1 bound to mAb specific for four distinct ICAM-1 epitopes localized in domains D1, D2, D4, and D5, and displayed similar molecular size properties as recombinant soluble ICAM-1 on FPLC size-exclusion chromatography. When immobilized via a domain D5-specific mAb, cICAM-1 mediated function (LFA-1)-dependent lymphocyte adhesion equivalent to sICAM-1. These data indicate that cICAM-1 contains most, if not all, of the five extracellular domains of membrane ICAM-1, as well as the ability to bind specifically to LFA-1. The cellular source of cICAM-1 appeared to be from mononuclear cells; only lymphoid cell lines or primary PBMC cultures had detectable levels of cICAM-1 in cell culture supernatants. Because cICAM-1 retains the ability to bind specifically to LFA-1, it may act to regulate cell adhesion by promoting de-adhesion. Alternatively, cICAM-1 may be the indirect consequence of inflammation or tissue damage. As such, the detection of cICAM-1 could be useful as a marker of inflammatory disease.
Boehringer Ingelheim Pharmaceuticals, Inc., Department of Immunology, Ridgefield, CT 06877.
R
R
Rothlein
E A
EA
Mainolfi
M
M
Czajkowski
S D
SD
Marlin
D015703:Antigens, CD / Q000378:metabolism*; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D015394:Molecular Structure; D008970:Molecular Weight; D012995:Solubility
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1