Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 725

11.5.7.3 Carboxyalkylpyrrole Protein Adducts

Inflammation leads to the release of oxidized phospholipids that activate Toll-like
receptor TLR2 on endothelial cells and provoke angiogenesis (Chap. 10 ). During
tissue repair, leukocytes contribute to the production of carboxyalkylpyrrole protein
adducts (CAP), such as

-2-carboxyethyl pyrrole (CEP) [ 1329 ] (Sect. 10.6.15 ).
These adducts, CEP in particular, promote angiogenesis.

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11.5.8 Inflammatory Diseases

The migration patterns of activated immunocytes depend on the stimulus features.
Innate bone marrow-derived immunocytes react to inflammatory signals, whereas
naive thymus-derived T lymphocytes poorly respond to such cues. Neutrophils are
often twinned to T H1 cells in inflammatory infiltrates. 59 Eosinophils participate in
inflammation that implicates T H2 cells. 60 Monocytes that differentiate to give birth
to macrophages or dendritic cells, are often involved in inflammatory lesions.
Inflamed endothelium undergoes changes in blood molecule permeability and
flowing cell adhesiveness. Chemoattractants trigger leukocyte adhesion to endothe-
lial cells and guide leukocyte migration and positioning. They mainly act via
G-protein-coupled receptors. Homing receptors are involved in the cell migration. 61
Except T and B lymphoblasts, which express adhesive integrins, circulating leuko-
cytes have inactive integrins. Leukocyte activation leads to active integrin, which
is able to bind to specific endothelial ligands. Integrin activation by endothelial
chemokines occurs very quickly (a few milliseconds).
Combinations of chemokines and GPCRs (Gi-RhoA and Rap1 pathways mainly)
activate endothelium adhesion under shear. L-selectin, expressed on most cir-
culating leukocytes, initiates leukocyte extravasation in venular endothelium in
inflammatory sites. Selectin-P and -E are inducibly produced by stimulated endothe-
lial cells to attract neutrophils, eosinophils, monocytes, natural killer cells, and T and
B lymphocytes. Moreover, L-selectin on circulating leukocytes can also bind surface
molecules (such as P-selectin glycoprotein ligand-1) on wall-adherent leukocytes,
enhancing the extravasation rate.

59 T H1 -based inflammation is characterized by tissue infiltration of interferon-

γ -secreting, CD4 +

and CD8 T lymphocytes and activated macrophages.

60 Allergic inflammation is characterized by infiltration of T H2 cells. Eosinophils and mastocytes
secrete interleukin-4, -5, and -13.
61 Chemokines CCR4 and CCR8 may be involved in the displacement of T H2 cells and CXCR3,
CXCR6, and CCR5 in the T H1 -cell recruitment. Eosinophil uses CCR3 at sites of allergic
inflammation, and certain T H2 cells and monocytes CCR2 at sites of T H1 inflammation. Tissue-
specific homing receptors, such as CCR10 for the skin and CCR9 for the gut explain the specificity
of leukocyte recruitment.

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