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 granulo mas induced by bead-immobilized mycobacterial purified protein derivative o r Schistosoma mansoni egg antigens, Where possible, CK protein levels were also measured, In addition, we examined effects of in vivo cytokine depleti ons. Findings were as follows: 1) bead challenge induced Increases In 18 of 24 CK transcripts with type-1 and type-2 responses displaying different pa tterns. CKs fell into four categories: a) type-1-dominant (gamma -interfero n-inducible protein (IP-10), monokine Induced by INF-gamma (MIG), macrophag e inflammatory protein-2 (MIP-2), lipopolysaccharide-induced chemokine (LIX ), rodent growth-related oncogene homologue (KP), macrophage inflammatory p rotein-1 alpha (MIP-1 alpha) and -1 beta (MIP-1 beta), lymphotactin), b) ty pe-2-dominant (eotaxin, monocyte chemotactic protein-2 (MCP-2) and -3 (MCP- 3), liver and activation-regulated chemokine (LARC), T cell activation prot ein-3 (TCA-3), c) type-1 and type-2 co-dominant (MCP-1, MCP-5, monocyte-der ived 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 pro duced maximally within 1 to 2 days. Others (MCP-2, MCP-3, eotaxin, lymphota ctin, LARC, TCA-3) displayed peak expression later. 3) Interferon-gamma neu tralization profoundly abrogated MIG, but had Little effect on other CKs, T umor necrosis factor-alpha neutralization caused up to 50% reduction in a r ange of CKs, These findings indicate that type-1 and type-2 granulomas disp lay characteristic CK profiles with coordinated expression that is under cy tokine-mediated regulation.