β1 Integrin Is Not Essential for Hematopoiesis but Is Necessary for the T Cell-Dependent IgM Antibody Response

Lund University, 22185 Lund, Sweden.
Immunity (Impact Factor: 21.56). 04/2002; 16(3):465-77. DOI: 10.1016/S1074-7613(02)00281-9
Source: PubMed


Several experimental evidences suggested that beta1 integrin-mediated adhesion of hematopoietic stem cells (HSC) is important for their function in the bone marrow (BM). Using induced deletion of the beta1 integrin gene restricted to the hematopoietic system, we show that beta1 integrin is not essential for HSC retention in the BM, hematopoiesis, and trafficking of lymphocytes. However, immunization with a T cell-dependent antigen resulted in virtually no IgM production and an increased secretion of IgG in mutant mice, while the response to a T cell-independent type 2 antigen showed decreases in both IgM and IgG. These data suggest that beta1 integrins are necessary for the primary IgM antibody response.

Download full-text


Available from: Heinrich Korner, Aug 22, 2014
  • Source
    • "The lack of any apparent difference in epidermal proliferation in unwounded skin in K14-α9 integrin null mice suggested that α9β1 was not required for normal epidermal development. Not surprisingly, the phenotypes of the uninjured skin observed with our K14-α9β1 null mice were significantly less pronounced than those observed in skin specific knockout of the entire β1 integrin family (Brakebusch et al, 2002; Grose et al, 2002; Raghavan et al, 2000). The epithelial cells of control and K14-α9 null cornea and skin had similar proliferation indices. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The wound microenvironment comprises constituents, such as the extracellular matrix (ECM), that regulate with temporal and spatial precision, the migratory, proliferative, and contractility of wound cells. Prompt closure of the wound is an early and critical phase of healing and β1 integrins are important in this process. We previously reported a marked increase in integrin α9β1 expression in epidermal keratinocytes in cutaneous and corneal wounds. However, the functional role of keratinocyte α9β1 during re-epithelialization is unknown and analysis has been precluded by the lethal phenotype of integrin α9β1 knockout mice. We now report that in conditional integrin α9 knockout (K14-α9 null) mice, normal proliferation occurs in epidermal keratinocytes and corneal basal cells. Normal epidermal keratinocyte morphology is also retained. However, corneal basal cell morphology and epithelial thickness are altered, suggesting that loss of integrin α9β1 results in abnormal corneal differentiation. In cutaneous wounds, the number of proliferating epidermal keratinocytes is significantly reduced in K14-α9 null mice compared with α9fl/− mice, but not in Cre (control) mice. The decreased keratinocyte proliferation observed in K14-α9 null mice negatively impacts healing, resulting in a thinner migrating epithelium, demonstrating that α9β1 is crucial for efficient and proper re-epithelialization during cutaneous wound healing.
    Full-text · Article · Jan 2009 · Journal of Investigative Dermatology
  • Source
    • "In the first set of experiments, we used mice carrying a b1-integrin gene flanked by loxP sites (b1-integrin floxed mice) (Figure 2A) (Brakebusch et al., 2002). In this mouse strain, the excision of the floxed b1-integrin gene can be confirmed by the activation of a reporter LacZ gene, which was inserted downstream of the b1-integrin locus. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis. In a manner comparable to hematopoietic stem cell transplantation, SSCs colonize the niche of recipient testes and reinitiate spermatogenesis following microinjection into the seminiferous tubules. However, little is known about the homing mechanism of SSCs. Here we examined the role of adhesion molecules in SSC homing. SSCs isolated from mice carrying loxP-tagged beta1-integrin alleles were ablated for beta1-integrin expression by in vitro adenoviral cre transduction. The beta1-integrin mutant SSCs showed significantly reduced ability to recolonize recipient testes in vivo and to attach to laminin molecules in vitro. In contrast, genetic ablation of E-cadherin did not impair homing, and E-cadherin mutant SSCs completed normal spermatogenesis. In addition, the deletion of beta1-integrin on Sertoli cells reduced SSC homing. These results identify beta1-integrin as an essential adhesion receptor for SSC homing and its association with laminin is critical in multiple steps of SSC homing.
    Preview · Article · Dec 2008 · Cell stem cell
  • Source
    • "The number of polymorphonuclear and mononuclear cells in the blood 5 weeks and 4 months after knockout induction was found to be not significantly altered. Also, the number of progenitor cells in blood and bone marrow was not significantely altered (Brakebusch et al. 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Evidence indicates that the intercellular adhesion molecule-1 and its counter-receptor β2 integrin are cardioprotective proteins during myocardial ischaemia-reperfusion, but no data are available concerning the role of blood cell β1 integrins in this process. We studied the effects of temporary myocardial ischaemia and reperfusion in blood cell-restricted β1 integrin knockout mice (β1-/-). The left descending coronary artery in conditional β1-/- integrin (β1-/-), β1 integrin +/+ (β1+/+) and β1 integrin -/- bone marrow chimeric (β1-/- BM) mice was ligated for 30 min, followed by reperfusion of either 3 h or 3 weeks. Plasma levels of troponin T were evaluated as an index of cardiac cellular damage. The histological evaluation of tissue damage was performed with Haematoxylin and Eosin stained sections. Cell infiltrations in the ischaemic area were investigated by immunofluorescence studies. It was found that plasma troponin T was at a similar level in β1-/-, β1+/+ and β1-/- BM mice treated with 30 min ischaemia and 3 h reperfusion. Histological analysis showed that ischaemia-reperfusion resulted in marked myocardial injury in all groups of animals, but the damage score of the hearts was not significantly different between β1-/-, β1+/+ and β1-/- BM mice after 3 h of reperfusion following 30 min of ischaemia (2.8 ± 0.5, 2.6 ± 0.5 and 2.8 ± 0.6, respectively, n.s.). Furthermore, no difference in scar sizes in ischaemia-injured hearts was found 3 weeks after ischaemia. Semi-quantification of cells demonstrated that, compared with β1+/+ mice, the number of infiltrating neutrophils was significantly reduced in β1-/- and β1-/- BM mice, whereas MAC-1(CD11b/CD18)-positive cells in the ischaemic regions were similar in myocardial tissues of all groups. We conclude that absence of β1 integrin expression in haematopoietic cells results in reduced neutrophil infiltration in the ischaemic regions, but does not influence myocardial damage of ischaemic hearts.
    Preview · Article · Aug 2008 · Experimental Physiology
Show more