The role of MIP-1 alpha in inflammation and hematopoiesis.

Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a member of the C-C subfamily of chemokines, a large superfamily of low-molecular weight, inducible proteins that exhibit a variety of proinflammatory activities in vitro including leukocyte chemotaxis. MIP-1 alpha is a particularly interesting chemokine, because in addition to its proinflammatory activities, it inhibits the proliferation of hematopoietic stem cells in vitro and in vivo. Here, the biologic properties of MIP-1 alpha are reviewed in light of recent data on mice homozygous for a disruption of the MIP-1 alpha gene. The MIP-1 alpha null mice have no overt abnormalities of peripheral blood or bone marrow cells, indicating that MIP-1 alpha is not necessary for normal hematopoiesis. However, the MIP-1 alpha null mice have a mice have a reduced inflammatory reduced inflammatory response to influenza virus and are resistant to coxsackievirus-induced myocarditis. These data demonstrate that MIP-1 alpha is required for a normal inflammatory response to these viruses. Agent that inhibit the action of MIP-1 alpha may therefore prove useful for controlling inflammation in these and other settings.