Adhesion Molecules in Leukocytes and Their Reactivity - Adhesion Molecules - page 154

In addition to direct contact activation through adhesion molecules, neutrophils
are activated by soluble chemoattractants, most of which bind to GPCRs (Fu et al.
2007).

ADHESION MOLECULES ON EOSINOPHILS

Human blood eosinophils express two β 1 -integrin dimers, α 4 β 1 and α 6 β 1 , four β 2 -

integrins, α 4 β 7 . h e reactive pattern

of eosinophils is similar to that of neutrophils including rapid mobilization into the
asthmatic lung, interacting with a diversity of ligands on bronchial endothelium
and degranulation within tissues.
α 4 β 1 - and

α M β 2 , α L β 2 , α X β 2 , α D β 2 , and a β 7 -integrin,

β 2 -integrins are the two most important integrins mediating
eosinophil adhesion and movement.

α M

α 4 β 1 -integrin is ei ciently mobilized to the
eosinophil membrane following antigen recognition. Recognition of VCAM-1
mediated by

α 4 β 1 is an important selective mechanism by which eosinophils are
preferred over neutrophils in asthma. α 4 β 1 mediates rolling, i rm adhesion and

migration of eosinophils to VCAM-1 potentiating granule release and generation
of superoxide anions. h e β 1 subunit localizes in podosomes and binds eosinophil

to VCAM-1, ICAM-1, i brinogen, vitronectin or albumin. β 2 is present on

peripheral blood eosinophils in conformational state that is constitutively less active
than

α M

α 4 β 1 . Eosinophils from peripheral blood do not easily adhere or migrate on
the ligands presumably because the dominating conformation of integrins on the
cell membrane is inactive and closed (Fig. 2) . Conformation-sensitive antibodies
showed that treatment of eosinophils with IL-5 and TNF- changed the shape of

integrins, converting them from bend and low ai nity shape into the extended and
opened, exposing the activation-induced epitope in the N-terminal region of

α

β 1 -
integrin. Exposure of the activation-induced epitope is important in movement of
primed blood eosinophils out in the circulation and into the airways in response
to segmental antigen challenge. h e activation of integrins on eosinophils can
be achieved following incubation of blood with IL-5, GM-CSF, fMLP, or platelet
activating factor in a GPCR-dependent mechanism. α 4 β 7 of blood eosinophils

supports static adhesion on MAdCAM-1 and mediates rolling on MAdCAM-1
and VCAM-1 under l ow. Cross-linking of β 7 on eosinophils by soluble VCAM-1

increases eosinophil survival in the airway lumen.

ADHESION MOLECULES ON T AND B LYMPHOCYTES

Unlike other leukocyte types, lymphocytes do not make stable focal adhesion
and focal complexes. Role of adhesion molecules T and B cells have been mainly
studied in dif erentiation, organ-specii c trai cking, and antigen presentation.
h e level of L-selectin expression is shown as a major recognition marker
regulating retention of lymphocytes in bone marrow and migration into the