{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:19:35Z","timestamp":1790885975250,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,12,8]],"date-time":"2005-12-08T00:00:00Z","timestamp":1134000000000},"content-version":"vor","delay-in-days":4846,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1992,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phytohemagglutinin (PHA) injection induces transient protease\u2010sensitive traffic of lymphocytes in skin and other tissues in several species. Examination of the possible roles of cytokines in such reactions showed that recombinant bovine and human tumor necrosis factor (TNF)\u2010\u03b1 potently induce dose\u2010dependent lymphocyte traffic in pig skin (and in other tissues including the draining lymph nodes) with early kinetics and a morphology of the inflammatory reaction similar to that of PHA (peaking 9\u201312 h). Recombinant human interleukin (IL)\u20101\u03b1 also induces dose\u2010dependent lymphocyte traffic, but it peaks at 4 h. Entry of labeled lymphocytes into inflammatory sites induced by PHA, TNF\u2010\u03b1 and IL\u20101\u03b1, but not into normal skin, is inhibited by approximately 80 % by their pretreatment with trypsin, indicative of the induction of endothelial determinants recognized by protease\u2010sensitive surface molecules on the lymphocytes. Even the minimal lymphocyte traffic induced by interferon\u2010\u03b3 and lipopolysaccharide was similarly protease sensitive. At the earliest stage (\u223c2 h) of significant induction of lymphocyte entry by TNF\u2010\u03b1 and IL\u20101\u03b1 the inductive signal for each appears easily saturated. Thus lymphocyte entry is little increased by increasing low cytokine doses over 100\u2010fold: However, these reactions are additive, and this was used to confirm that they are distinct from each other and from PHA. A further distinction was revealed by the homing of lymphocytes pretreated with pertussis toxin: such lymphocytes were &gt;90 % inhibited in their homing to tissues through constitutive high endothelial venules (HEV) and &gt;60 % inhibited in homing to TNF\u2010\u03b1 and IL\u20101\u03b1 skin sites, but unaffected in homing to PHA skin sites (like most non\u2010HEV\u2010mediated traffic). Moreover, potent chicken anti\u2010TNF\u2010\u03b1, which prevented TNF\u2010induced lymphocyte entry, did not affect PHA\u2010induced traffic. Thus, these three agents which induce peripheral lymphocyte traffic appear to involve different mechanisms as shown by differences in (i) their kinetics; (ii) the effect of anti\u2010TNF\u2010\u03b1 and (iii) the effect of pertussis toxin treatment of the lymphocytes and by the fact that their inductive mechanisms are additive in effect.<\/jats:p>","DOI":"10.1002\/eji.1830220903","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T17:49:44Z","timestamp":1172771384000},"page":"2195-2203","source":"Crossref","is-referenced-by-count":25,"title":["Active lymphocyte traffic induced in the periphery by cytokines and phytohemagglutinin: Three different mechanisms?"],"prefix":"10.1002","volume":"22","author":[{"given":"Richard M.","family":"Binns","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T.","family":"Licence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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