PMID- 11159181 OWN - NLM STAT- MEDLINE DCOM- 20010405 LR - 20240413 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 158 IP - 2 DP - 2001 Feb TI - Differential and sequential expression of multiple chemokines during elicitation of allergic contact hypersensitivity. PG - 431-40 AB - Regulation of chemokine-mediated leukocyte migration within inflammatory tissues is a complex event that cannot be mimicked and analyzed in vitro. We therefore investigated the role of macrophage- and T-lymphocyte-specific chemoattractants involved in the positioning of immune effector cells during the elicitation phase of contact hypersensitivity, a prototype of a T-lymphocyte-mediated immune reaction. Serial sections of skin biopsies obtained from sensitized individuals at distinct time intervals after epicutaneous application of allergens were hybridized with anti-sense probes of a large panel of chemokines or immunohistologically labeled with leukocyte-specific antibodies. Multifocal expression of monocyte chemoattractant protein-1 (MCP-1) was already detected after 6 hours in basal keratinocytes clearly preceding the infiltration of monocytes and T cells. Increasing basal expression of MCP-1 and, in addition, of regulated upon activation, normal T-cell expressed and secreted (RANTES) after 12 hours was accompanied by dermal expression of MCP-1, macrophage-derived chemoattractant (MDC), and RANTES and paralleled by infiltration of mononuclear cells into dermis and epidermis. Expression of the T-lymphocyte-specific chemokines IP-10 and MIG in epidermis and dermis and of MDC, pulmonary and activation-regulated chemokine (PARC), and thymus and activation-regulated chemokine (TARC) exclusively in the dermis started after 12 hours reaching maximum levels at 72 hours and was associated with infiltration of T cells into the epidermal compartment. Our data provide evidence that migrating effector cells encounter multiple chemoattractant signals in a complex spatial and temporal pattern. In particular, keratinocytes contribute to the vigorous immigration by sequential expression of MCP-1, RANTES, and interferon-inducible protein-10 (IP-10) monokine induced by gamma interferon (MIG), indicating that chemokine-mediated nonimmunological mechanisms precede and corroborate antigen-specific mechanisms during elicitation of contact hypersensitivity. FAU - Goebeler, M AU - Goebeler M AD - Department of Dermatology, University of Wurzburg Medical School, Wurzburg, Germany. FAU - Trautmann, A AU - Trautmann A FAU - Voss, A AU - Voss A FAU - Brocker, E V AU - Brocker EV FAU - Toksoy, A AU - Toksoy A FAU - Gillitzer, R AU - Gillitzer R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Allergens) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CCL17 protein, human) RN - 0 (CCL18 protein, human) RN - 0 (CD3 Complex) RN - 0 (CD68 antigen, human) RN - 0 (CXCL9 protein, human) RN - 0 (Chemokine CCL17) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Chemokine CXCL10) RN - 0 (Chemokine CXCL9) RN - 0 (Chemokines) RN - 0 (Chemokines, CC) RN - 0 (Chemokines, CXC) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (RNA, Messenger) SB - IM MH - Allergens/administration & dosage/immunology MH - Antigens, CD/analysis MH - Antigens, Differentiation, Myelomonocytic/analysis MH - CD3 Complex/analysis MH - Chemokine CCL17 MH - Chemokine CCL2/genetics MH - Chemokine CCL5/genetics MH - Chemokine CXCL10 MH - Chemokine CXCL9 MH - Chemokines/*genetics MH - Chemokines, CC/genetics MH - Chemokines, CXC/genetics MH - Dermatitis, Allergic Contact/*genetics/immunology MH - Gene Expression Regulation/drug effects MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization MH - *Intercellular Signaling Peptides and Proteins MH - Macrophages/immunology/metabolism MH - RNA, Messenger/drug effects/genetics/metabolism MH - Skin/immunology/metabolism/pathology MH - T-Lymphocytes/immunology/metabolism MH - Time Factors PMC - PMC1850305 EDAT- 2001/02/13 11:00 MHDA- 2001/04/06 10:01 PMCR- 2001/08/01 CRDT- 2001/02/13 11:00 PHST- 2001/02/13 11:00 [pubmed] PHST- 2001/04/06 10:01 [medline] PHST- 2001/02/13 11:00 [entrez] PHST- 2001/08/01 00:00 [pmc-release] AID - S0002-9440(10)63986-7 [pii] AID - 2519 [pii] AID - 10.1016/s0002-9440(10)63986-7 [doi] PST - ppublish SO - Am J Pathol. 2001 Feb;158(2):431-40. doi: 10.1016/s0002-9440(10)63986-7.