Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 708

11.5.3 Crossing of the Vascular Basement Membrane

After transendothelial migration, leukocytes cross the vascular basement membrane.
The venular basement membrane that has low content of matrix protein is a
preferential site for neutrophil and monocyte migration under a CCL2 chemotactic
gradient [ 1445 ]. Leukocyte migration across the perivascular basement membrane
involves

α 6 -integrins and PECAM-1 [ 1445 ].
Each leukocyte subtype uses a different mechanism to cross the vascular base-
ment membrane. Neutrophils enlarge regions of low-protein content and degrade
laminin [ 1445 ]. Monocytes can use pre-existing smaller permeable regions of the
basement membrane due to their higher deformability.

11.5.4 Interstitial Migration of Leukocytes

Migratory behavior differs between neutrophils and monocytes. Monocytes begin
their interstitial migration later and are slower than neutrophils [ 1444 ]. Neutrophil
migration in conjonctive tissue involves

β 1 -integrin.
Molecular guidance for selective recruitment into certain tissues depends on
some environmental factors. Vitamin-A and -D3 influence lymphocyte homing to
small intestine and epidermis [ 1445 ]. Dendritic cells intervene in the transformation
of vitamin precursors into active derivatives such as retinoic acid.

11.5.5 Molecular Mechanisms of Leukocyte Chemotaxis

Once leukocytes have crossed the vascular endothelium, they integrate and prioritize
multiple combinatorial chemotactic signals, using PI3K c1γ kinase as well as PTen

and SHIP1 phosphatase, among others.

11.5.5.1 Phosphatidylinositol 3-Kinase

Chemotactic gradient signal received by specific G-protein-coupled receptors on the
surface of leukocytes is transduced and amplified within the cell. Phosphatidylino-
sitol 3-kinase is activated in the cell region that faces the chemoattractant [ 1444 ]. It
then phosphorylates phosphatidylinositol (4,5)-bisphosphate to produce phosphati-
dylinositol trisphosphate. PIP 3 -binding proteins then accumulate in the pseudopods
of migrating cells. Simultaneously, enzymes that degrade PIP 3 are active on the cell
sides and uropod, thereby neutralizing PI3K activity in these regions. Phosphatase
PTen dephosphorylates PIP 3 into PI(4,5)P 2 . Src homology-2 domain-containing