HUMAN MACROPHAGE INFLAMMATORY PROTEIN-ALPHA (MIP-1-ALPHA) AND MIP-1-BETA CHEMOKINES ATTRACT DISTINCT POPULATIONS OF LYMPHOCYTES

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 selectins 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 1alpha (MIP-1alpha) and MIP-1beta, do not share identical attractant activities for lymphocyte subpopulations. When analyzed in vitro in microchemotaxis experiments, HuMIP-1beta tends to attract CD4+ T lymphocytes, with some preference for T cells of the naive (CD45RA) phenotype. HuMIP-1alpha, when tested in parallel with HuMIP-1beta, is a more potent lymphocyte chemoattractant with a broader range of concentration-dependent chemoattractant specificities. HuMIP-1alpha 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-1alpha and -1beta have differential attractant activities for subsets of immune effector cells, with HuMIP-1alpha having greater effects than HuMIP-1beta, particularly on B cells.