Differential and sequential expression of multiple chemokines during elicitation of allergic contact hypersensitivity.
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.
Goebeler
M
M
Department of Dermatology, University of Würzburg Medical School, Würzburg, Germany.
Trautmann
A
A
Voss
A
A
Bröcker
E V
EV
Toksoy
A
A
Gillitzer
R
R
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D054414:Chemokine CCL17; D018932:Chemokine CCL2 / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines / Q000235:genetics*; D019742:Chemokines, CC / Q000235:genetics; D019743:Chemokines, CXC / Q000235:genetics; D017449:Dermatitis, Allergic Contact / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D000097382:CD68 Molecule
D000485:Allergens; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D054414:Chemokine CCL17; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C106230:CCL17 protein, human; C111792:CCL18 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C080810:CXCL9 protein, human