Abstract
Lymphocyte trafficking is an essential process in immune and inflammatory functions which can be thought to contain at least two main components: adhesion and migration. Whereas adhesion molecules such as the selections are known to mediate the homing of leukocytes from the blood to the endothelium, the chemoattractant substances responsible for the migration of specific subsets of lymphocytes to sites of infection or inflammation are largely unknown. Here we show that two molecules in the chemokine (for chemoattractant cytokine) superfamily, human macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta, do not share identical attractant activities for lymphocyte subpopulations. When analyzed in vitro in microchemotaxis experiments, HuMIP-1 beta tends to attract CD4+ T lymphocytes, with some preference for T cells of the naive (CD45RA) phenotype. HuMIP-1 alpha, when tested in parallel with HuMIP-1 beta, is a more potent lymphocyte chemoattractant with a broader range of concentration-dependent chemoattractant specificities. HuMIP-1 alpha at a concentration of 100 pg/ml attracts B cells and cytotoxic T cells, whereas at higher concentrations (10 ng/ml), the migration of these cells appears diminished, and the migration of CD4+ T cells is enhanced. Thus, in this assay system, HuMIP-1 alpha and -1 beta have differential attractant activities for subsets of immune effector cells, with HuMIP-1 alpha having greater effects than HuMIP-1 beta, particularly on B cells.
MeSH Terms
Chemokine CCL3
Chemokine CCL4
Chemokine CCL5
Chemotactic Factors/pharmacology
Chemotaxis, Leukocyte
Cytokines/pharmacology
Humans
Lymphocytes/drug effects,immunology
Lymphokines/pharmacology
Macrophage Inflammatory Proteins
Monokines/pharmacology
Recombinant Proteins/pharmacology
Chemicals
Chemokine CCL3
Chemokine CCL4
Chemokine CCL5
Chemotactic Factors
Cytokines
Lymphokines
Macrophage Inflammatory Proteins
Monokines
Recombinant Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Schall T J
Genentech, Inc., South San Francisco, California 94080.
Bacon K
Camp R D
Kaspari J W
Goeddel D V
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