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| Biology of chemokine and classical chemoattractant receptors: Differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells |
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| Author(s): Campbell JJ, Qin SX, Bacon KB, Mackay CR, Butcher EC |
| Source: JOURNAL OF CELL BIOLOGY Volume: 134 Issue: 1 Pages: 255-266 Published: JUL 1996 |
| Times Cited: 172 References: 47 |
| Abstract: Several chemoattractant receptors can support agonist-induced, integrin-dependent arrest of rolling neutrophils in inflamed venules in vivo, as well as subsequent crawling into tissues, It has been hypothesized that receptors of the G alpha(1)-linked chemoattractant subfamilies, especially receptors for chemokines, may mediate parallel activation-dependent arrest of homing lymphocyte subsets. However, although several chemokines can attract subsets of B or T cells, robust chemoattractant triggering of resting lymphocyte adhesion to vascular ligands has not been observed. To study the biology of individual leukocyte chemoattractant receptors in a defined lymphoid environment, mouse L1/2 pre-B cells and/or human Jurkat T cells were transfected with alpha (IL-8 receptor A) or beta (MIP-1 alpha/CC-CKR-1) chemokine receptors, or with the classical chemoattractant C5a (C5aR) or formyl peptide receptors (fPR). All receptors supported robust agonist-dependent alpha 4 beta 1 integrin-mediated adhesion of lymphocytes to VCAM-1, L1/2 cells cotransfected with fPR and beta 7 integrin were also induced to bind MAdCAM-1, suggesting common mechanisms coupling chemoattractant receptors to activation of distinct integrins, Adhesion was rapid but transient, with spontaneous reversion to unstimulated levels within 5 min after peak binding. When observed under flow conditions, alpha 4 beta 1-mediated arrest occurred within seconds after initiation of contact and rolling of IL-8RA transfectants on a VCAM-1/IL-8 co-coated surface; and arrest reversed spontaneously after a mean of 5 min with a return to rolling behavior. Each of the receptors also conferred agonist-specific chemotaxis; however, whereas strong adhesion required simultaneous occupancy of many receptors with maximal responses above the K-d, chemotaxis in each case was suppressed at high agonist concentrations. The findings indicate that alpha and beta chemokine as well as classical chemoattractant receptors can trigger robust adhesion as well as directed migration of lymphoid cells, but that the requirements for and kinetics of adhesion triggering and chemotaxis are distinct, thus permitting their independent regulation. They suggest that the discordance between proadhesive and chemoattractant responses of circulating lymphocytes to many chemokines may reflect quantitative aspects of receptor expression and/or coupling rather than qualitative differences in receptor signaling. |
| Document Type: Article |
| Language: English |
| Reprint Address: Campbell, JJ (reprint author), STANFORD UNIV, SCH MED, DEPT PATHOL, LAB IMMUNOL & VASC BIOL, STANFORD, CA 94305 USA |
Addresses:
1. STANFORD UNIV, SCH MED, DEPT MED, CTR DIGEST DIS, STANFORD, CA 94305 USA
2. VET AFFAIRS PALO ALTO HLTH CARE SYST, FOOTHILL RES CTR, CTR MOLEC BIOL & MED, PALO ALTO, CA 94304 USA
3. LEUKOSITE INC, CAMBRIDGE, MA 02142 USA
4. DNAX RES INST MOLEC & CELLULAR BIOL INC, PALO ALTO, CA 94304 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Cell Biology |
| IDS Number: UW676 |
| ISSN: 0021-9525 |
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