Chemokine expression dynamics in mycobacterial (type-l) and schistosomal (type-2) antigen-elicited pulmonary granuloma formation

Transcript expression of 24 chemokines (CKs) was examined throughout 8 days in mouse lungs with type-1 (Th1) or type-2 (Th2) cytokine-mediated granulomas induced by bead-immobilized mycobacterial purified protein derivative or Schistosoma mansoni egg antigens, Where possible, CK protein levels were also measured, In addition, we examined effects of in vivo cytokine depletions. Findings were as follows: 1) bead challenge induced Increases In 18 of 24 CK transcripts with type-1 and type-2 responses displaying different patterns. CKs fell into four categories: a) type-1-dominant (gamma -interferon-inducible protein (IP-10), monokine Induced by INF-gamma (MIG), macrophage inflammatory protein-2 (MIP-2), lipopolysaccharide-induced chemokine (LIX), rodent growth-related oncogene homologue (KP), macrophage inflammatory protein-1 alpha (MIP-1 alpha) and -1 beta (MIP-1 beta), lymphotactin), b) type-2-dominant (eotaxin, monocyte chemotactic protein-2 (MCP-2) and -3 (MCP-3), liver and activation-regulated chemokine (LARC), T cell activation protein-3 (TCA-3), c) type-1 and type-2 co-dominant (MCP-1, MCP-5, monocyte-derived chemokine (MDC), thymus and activation-related chemokine (TARC), C10), and d) constitutive (lungkine, secondary lymphoid-tissue chemokine (SLC), EBI1-ligand chemokine (ELC), fractalkine, macrophage inflammatory protein-1 gamma (MIP1-gamma), and stromal cell derived factor-1 alpha (SDF1-alpha), 2) CKs displayed characteristic temporal patterns. CXC (IP-10, MIG, MIP-2, LM, KC) and certain CC (MCP-I, MCP-5, MIP-1 alpha, MIP-1 beta) CKs were produced maximally within 1 to 2 days. Others (MCP-2, MCP-3, eotaxin, lymphotactin, LARC, TCA-3) displayed peak expression later. 3) Interferon-gamma neutralization profoundly abrogated MIG, but had Little effect on other CKs, Tumor necrosis factor-alpha neutralization caused up to 50% reduction in a range of CKs, These findings indicate that type-1 and type-2 granulomas display characteristic CK profiles with coordinated expression that is under cytokine-mediated regulation.