Direct evidence for two affinity states for lymphocyte function-associated antigen 1 on activated T cells.

Lymphocytes activated by antigen receptor cross-linking or phorbol esters adhere avidly to surfaces bearing intercellular adhesion molecule 1 (ICAM-1) through the adhesion receptor lymphocyte function-associated antigen 1 (LFA-1). It is not known whether avid adhesion by stimulated lymphocytes is due to higher affinity binding of ICAM-1 or due solely to post-receptor mechanisms. We have used a recombinant, soluble form of the ICAM-1 molecule to measure the affinity of binding to LFA-1 on unstimulated T cells and T cells stimulated with phorbol esters. The affinity was found to be too low for direct measurements, requiring instead the use of competition protocols in which ICAM-1 competes for binding with radiolabeled Fab from a monoclonal antibody specific for LFA-1. By analysis of the equilibrium and kinetics of competitive binding, we found that the affinity on unstimulated T cells is very low, about 100 microM. Activation of the T cells by phorbol esters caused a small increase in average binding affinity. Further analysis suggested that the change in average affinity reflected the conversion of a fraction of LFA-1 molecules to a state with a 200-fold higher affinity.

Heterotypic adherence between murine leukemia/lymphoma cells and marrow stromal cells involves a recognition mechanism with galactosyl and mannosyl specificities.

We have previously shown that leukemia/lymphoma (LL) cells adhere to marrow stromal cells (MSC), and MSC induce clonal growth of LL cells. Even though CD11a/18 and CD54 are important in leukocyte and endothelial cell interaction, the literature suggested that these adhesion proteins are not involved in adhesion of hematopoietic stem cells to MSC. We therefore utilized a unique ICAM-1- murine MSC line (MLT) to evaluate the mechanisms of adherence of LL cells (L5178Y and L1210) to MLT. Adherence of LL cells to extracellular matrix (ECM) proteins was also examined. L1210 cells attached to collagen types III and IV, laminin, and fibronectin, but not to collagen type I. L5178Y cells did not attach to any of the ECM proteins tested. The adherence of both L1210 and L5178Y to MSC was unaffected by rat monoclonal antibodies to murine CD11a, CD11b, and CD18. Neoglycoprotein probes, mannosyl-bovine serum albumin (BSA) and galactosyl-BSA, inhibited the adherence of L5178Y and L1210 cells to MSC by 34%-63% of controls at concentrations of 10(-3) and 5 x 10(-3) M. In contrast, fucosyl-BSA had no inhibitory effect on LL cell adherence of MLT. These data suggest that 1) LL cells may adhere to MSC by a lectin mechanism with mannosyl and galactosyl specificities; and 2) other mechanisms of adherence, not yet defined, are also important in this system.

School management and contingency theory: an emerging perspective.

In an article written for educational administrators, Hanson explains the assumptions, framework, and application of contingency theory. The author sees contingency theory as a way for organizations to adapt to uncertainty by developing a strategic plan with alternative scenarios. He urges school administrators to join businessmen and public managers in using a technique described as "the most powerful current sweeping over the organizational field." The theory assumes that: (1) a maze of goals govern the development of events; (2) different management approaches may be appropriate within the same organization; and (3) different leadership styles suit different situations. Contingency planning helps the organization to respond to uncertainty in the external environment by identifying possible events that may occur and by preparing alternative stratgies to deal with them. Hanson describes the purpose of this process as providing "a more effective match between an organization and its environment." He explains that contingency theory analyzes the internal adjustments of the organization (e.g., decision making process, structure, technology, instructional techniques) as it seeks to meet the shifting demands of its external or internal environments. According to the author, the intent of contingency theory is to establish an optimal "match" between environmental demands (and support) and the response capabilities of the organization including its structure, planning process, and leadership style.