Limits...
Matrix valency regulates integrin-mediated lymphoid adhesion via Syk kinase.

Stupack DG, Li E, Silletti SA, Kehler JA, Geahlen RL, Hahn K, Nemerow GR, Cheresh DA - J. Cell Biol. (1999)

Bottom Line: Nonactivated lymphoid cells attach preferentially to polymerized ECM proteins yet are unable to attach to monomeric forms or fragments of these proteins without previous activation.Adhesion of nonactivated lymphoid cells to polymeric ECM components results in activation of the antigen receptor-associated Syk kinase that accumulates in adhesion-promoting podosomes.In fact, activation of Syk by antigen or agonists, as well as expression of an activated Syk mutant in lymphoid cells, facilitates their adhesion to monomeric ECM proteins or their fragments.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

ABSTRACT
Lymphocytes accumulate within the extracellular matrix (ECM) of tumor, wound, or inflammatory tissues. These tissues are largely comprised of polymerized adhesion proteins such as fibrin and fibronectin or their fragments. Nonactivated lymphoid cells attach preferentially to polymerized ECM proteins yet are unable to attach to monomeric forms or fragments of these proteins without previous activation. This adhesion event depends on the appropriate spacing of integrin adhesion sites. Adhesion of nonactivated lymphoid cells to polymeric ECM components results in activation of the antigen receptor-associated Syk kinase that accumulates in adhesion-promoting podosomes. In fact, activation of Syk by antigen or agonists, as well as expression of an activated Syk mutant in lymphoid cells, facilitates their adhesion to monomeric ECM proteins or their fragments. These results reveal a cooperative interaction between signals emanating from integrins and antigen receptors that can serve to regulate stable lymphoid cell adhesion and retention within a remodeling ECM.

Show MeSH

Related in: MedlinePlus

Colocalization of  LCL attachment with fibrin  deposition in tissue sections.  (A) Serial cryosections of a  human breast tumor were  stained with hematoxylin and  eosin or (B) stained with  mAb 17B4, a monoclonal  antibody specific for fibrin  (10 μg/ml) as detected with  secondary rhodamine-conjugated goat anti–mouse polyclonal antibody (red). Fluorescent-labeled LCL (105/ slide) were allowed to attach  to immediate serial sections  in DME, 3% BSA, 100 U/ml  heparin and either 50 μg/ml  nonspecific murine IgG (C)  or monoclonal antibody  LM609 (anti-αvβ3) (D). Attached cells per field in the  presence of control, LM609,  or P1F6 (anti-αvβ5) antibodies were quantified by direct  counting of fluorescent cells  (E). Results are expressed  as the mean ± SE of six  fields counted. A representative experiment of three is  shown.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2132930&req=5

Figure 1: Colocalization of LCL attachment with fibrin deposition in tissue sections. (A) Serial cryosections of a human breast tumor were stained with hematoxylin and eosin or (B) stained with mAb 17B4, a monoclonal antibody specific for fibrin (10 μg/ml) as detected with secondary rhodamine-conjugated goat anti–mouse polyclonal antibody (red). Fluorescent-labeled LCL (105/ slide) were allowed to attach to immediate serial sections in DME, 3% BSA, 100 U/ml heparin and either 50 μg/ml nonspecific murine IgG (C) or monoclonal antibody LM609 (anti-αvβ3) (D). Attached cells per field in the presence of control, LM609, or P1F6 (anti-αvβ5) antibodies were quantified by direct counting of fluorescent cells (E). Results are expressed as the mean ± SE of six fields counted. A representative experiment of three is shown.

Mentions: Lymphoid cells can be detected in association with the ECM of tumor and inflammatory tissues. Fibrin, a polymeric constituent of tumor ECM (Dvorak et al., 1995), is recognized by integrin αvβ3 expressed on a subpopulation of lymphoid cells (Halvorson et al., 1996). To examine lymphoid interaction with a tumor-associated ECM, nonactivated lymphoblastoid B cells (LCL) were assessed for their attachment to fibrin-rich cryosections of human breast tumors (Fig. 1, A and B). LCL attachment localized to regions of fibrin deposition (Fig. 1 C), and the observed adhesion was significantly blocked (Fig. 1 D) with monoclonal (mAb) LM609 directed to integrin αvβ3 (∼65%, Fig. 1 E), a known receptor for fibrinogen/fibrin (Cheresh, 1987) (and other provisional ECM components) expressed on LCL. However, these tissues also contain other adhesive ligands for integrin αvβ3. Thus, fibrin does not account for all the adhesive interactions observed.


Matrix valency regulates integrin-mediated lymphoid adhesion via Syk kinase.

Stupack DG, Li E, Silletti SA, Kehler JA, Geahlen RL, Hahn K, Nemerow GR, Cheresh DA - J. Cell Biol. (1999)

Colocalization of  LCL attachment with fibrin  deposition in tissue sections.  (A) Serial cryosections of a  human breast tumor were  stained with hematoxylin and  eosin or (B) stained with  mAb 17B4, a monoclonal  antibody specific for fibrin  (10 μg/ml) as detected with  secondary rhodamine-conjugated goat anti–mouse polyclonal antibody (red). Fluorescent-labeled LCL (105/ slide) were allowed to attach  to immediate serial sections  in DME, 3% BSA, 100 U/ml  heparin and either 50 μg/ml  nonspecific murine IgG (C)  or monoclonal antibody  LM609 (anti-αvβ3) (D). Attached cells per field in the  presence of control, LM609,  or P1F6 (anti-αvβ5) antibodies were quantified by direct  counting of fluorescent cells  (E). Results are expressed  as the mean ± SE of six  fields counted. A representative experiment of three is  shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2132930&req=5

Figure 1: Colocalization of LCL attachment with fibrin deposition in tissue sections. (A) Serial cryosections of a human breast tumor were stained with hematoxylin and eosin or (B) stained with mAb 17B4, a monoclonal antibody specific for fibrin (10 μg/ml) as detected with secondary rhodamine-conjugated goat anti–mouse polyclonal antibody (red). Fluorescent-labeled LCL (105/ slide) were allowed to attach to immediate serial sections in DME, 3% BSA, 100 U/ml heparin and either 50 μg/ml nonspecific murine IgG (C) or monoclonal antibody LM609 (anti-αvβ3) (D). Attached cells per field in the presence of control, LM609, or P1F6 (anti-αvβ5) antibodies were quantified by direct counting of fluorescent cells (E). Results are expressed as the mean ± SE of six fields counted. A representative experiment of three is shown.
Mentions: Lymphoid cells can be detected in association with the ECM of tumor and inflammatory tissues. Fibrin, a polymeric constituent of tumor ECM (Dvorak et al., 1995), is recognized by integrin αvβ3 expressed on a subpopulation of lymphoid cells (Halvorson et al., 1996). To examine lymphoid interaction with a tumor-associated ECM, nonactivated lymphoblastoid B cells (LCL) were assessed for their attachment to fibrin-rich cryosections of human breast tumors (Fig. 1, A and B). LCL attachment localized to regions of fibrin deposition (Fig. 1 C), and the observed adhesion was significantly blocked (Fig. 1 D) with monoclonal (mAb) LM609 directed to integrin αvβ3 (∼65%, Fig. 1 E), a known receptor for fibrinogen/fibrin (Cheresh, 1987) (and other provisional ECM components) expressed on LCL. However, these tissues also contain other adhesive ligands for integrin αvβ3. Thus, fibrin does not account for all the adhesive interactions observed.

Bottom Line: Nonactivated lymphoid cells attach preferentially to polymerized ECM proteins yet are unable to attach to monomeric forms or fragments of these proteins without previous activation.Adhesion of nonactivated lymphoid cells to polymeric ECM components results in activation of the antigen receptor-associated Syk kinase that accumulates in adhesion-promoting podosomes.In fact, activation of Syk by antigen or agonists, as well as expression of an activated Syk mutant in lymphoid cells, facilitates their adhesion to monomeric ECM proteins or their fragments.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

ABSTRACT
Lymphocytes accumulate within the extracellular matrix (ECM) of tumor, wound, or inflammatory tissues. These tissues are largely comprised of polymerized adhesion proteins such as fibrin and fibronectin or their fragments. Nonactivated lymphoid cells attach preferentially to polymerized ECM proteins yet are unable to attach to monomeric forms or fragments of these proteins without previous activation. This adhesion event depends on the appropriate spacing of integrin adhesion sites. Adhesion of nonactivated lymphoid cells to polymeric ECM components results in activation of the antigen receptor-associated Syk kinase that accumulates in adhesion-promoting podosomes. In fact, activation of Syk by antigen or agonists, as well as expression of an activated Syk mutant in lymphoid cells, facilitates their adhesion to monomeric ECM proteins or their fragments. These results reveal a cooperative interaction between signals emanating from integrins and antigen receptors that can serve to regulate stable lymphoid cell adhesion and retention within a remodeling ECM.

Show MeSH
Related in: MedlinePlus