Anti-Mouse MAdCAM-1 (MECA-89) – Purified in vivo PLATINUM^TM Functional Grade

Clone MECA-89 is commonly used in vivo in mice to neutralize or block MAdCAM-1 (Mucosal Addressin Cell Adhesion Molecule-1) function, which plays an essential role in immune cell trafficking, particularly in the context of gut and mucosal immunity. Researchers typically use MECA-89 in mouse models to study mechanisms of leukocyte homing, inflammation, and diseases affecting mucosal tissues.

Key in vivo applications of MECA-89 in mice include:

• Blocking MAdCAM-1-mediated lymphocyte trafficking: MECA-89 is administered to inhibit the interaction between MAdCAM-1 and its ligands (mainly integrin α4β7), thereby preventing immune cells from migrating into mucosal tissues like the gut and Peyer’s patches.
• Modeling inflammatory bowel diseases (IBD): By disrupting cell adhesion and trafficking, MECA-89 facilitates the study of pathogenesis, immune responses, and therapeutic targets in models of colitis and other forms of IBD.
• Examining the role of MAdCAM-1 in diabetes and insulitis: MECA-89 is used in NOD mice (diabetes-prone strain) to investigate the impact of MAdCAM-1 upregulation in peripheral lymph nodes and its involvement in autoimmune diabetes.
• Studies of mucosal immunity and lymphoid tissue development: By blocking MAdCAM-1, MECA-89 can be used to study lymphocyte homing to mucosal lymphoid tissues, the development of mucosal-associated lymphoid organs, and immune response regulation.
• Depletion experiments: Used to deplete or neutralize target cells or molecules in vivo to analyze immune processes or inflammatory responses.
• Supporting techniques: MECA-89 is applied for in vivo labeling, tissue staining, and flow cytometric analysis in live animals and tissue samples, although these are secondary to its functional blocking application.

Summary Table of Common In Vivo Applications of MECA-89 in Mice

MECA-89 is primarily regarded as a blocking antibody for MAdCAM-1, making it a foundational tool for dissecting immune cell migration and mucosal immune responses in mouse models.

Commonly used antibodies or proteins in combination with MECA-89 (anti-MAdCAM-1) in the literature include integrins (especially α4β7 integrin), other addressins, and standard immune markers such as CD45, B220, and CD40.

Key reagents and markers commonly used alongside MECA-89:

• α4β7 integrin: MAdCAM-1 is a primary ligand for this integrin, and studies frequently use α4β7 integrin-targeting antibodies to investigate mucosal lymphocyte homing and adhesion.
• Other addressins and selectin ligands:
  • MECA-367 and MECA-79: MECA-367 is another anti-MAdCAM-1 antibody, and MECA-79 recognizes the peripheral node addressin (PNAd) carbohydrate epitope, used to discriminate between different HEV (high endothelial venule) ligands.
  • CD62L (L-selectin): MAdCAM-1 also interacts with L-selectin, so antibodies against CD62L are sometimes included to study lymphocyte trafficking.
• Immune cell markers for flow cytometry and tissue immunostaining:
  • CD45 (pan-leukocyte marker)
  • CD40 (B cell activation)
  • B220 (B cell marker)
  • CD23, CD35 (associated with B cells and follicular dendritic cells)

These marker panels are often used in immune tissue studies, notably of mucosal lymphoid organs, Peyer's patches, or lymph node HEVs, to characterize both vascular structure and immune cell populations present in situ.

Summary table:

These combinations allow delineation of specific endothelial and leukocyte populations, study of lymphocyte homing, and functional differentiation within lymphoid tissues.

Key findings from scientific literature citing clone MECA-89 focus on two distinct research areas, due to ambiguity in the naming: immunological studies with the anti-MAdCAM-1 antibody (clone MECA-89) and studies on the mecA gene in Staphylococcus aureus. However, in antibody and cell biology literature, MECA-89 specifically refers to a rat monoclonal antibody targeting mouse MAdCAM-1, and this is the most likely context for your query.

Key findings from citations of clone MECA-89 (anti-MAdCAM-1 antibody) include:

• Specificity and Epitope Recognition: MECA-89 recognizes the second immunoglobulin domain of MAdCAM-1, differentiating it from MECA-367, which binds the N-terminal domain.
• Functional Effects: Unlike MECA-367, MECA-89 does not affect lymphocyte binding to MAdCAM-1 or block MAdCAM-1 binding to the α4β7 integrin in vitro.
• Impact on Adhesion: MECA-89 inhibits L-selectin-dependent rolling of lymphocytes in vivo, indicating a selective blockade of L-selectin interactions but not direct α4β7-mediated lymphocyte attachment. These findings help dissect the mechanisms of lymphocyte trafficking in mucosal immune responses.
• Expression Target: MAdCAM-1 is present on high endothelial venules of mucosal lymphoid organs and Peyer’s patches, as well as lamina propria venules, and MECA-89 has been widely used in immunofluorescence for delineating these vascular structures.
• Research Applications: MECA-89 is valuable in experimental models to study cell adhesion, lymphocyte homing, and the specialized roles of high endothelial venules in mucosal immunity.

Essential context:

• Distinction from Other Clones: MECA-89 and MECA-367 bind different domains of MAdCAM-1, allowing for functional dissection of MAdCAM-1-mediated processes.
• Non-Effect on α4β7: MECA-89’s lack of effect on α4β7 binding specifically points to its utility in isolating L-selectin–dependent mechanisms.
• Tools for Mouse Immunology: As a highly cited reagent, MECA-89 supports a wide range of anatomical and functional studies in mouse mucosal immunology.

Alternative context (less likely but present in search results):

• Some literature with similar nomenclature to MECA-89 refers to genetic studies on the mecA gene in MRSA; these findings involve the gene’s clonal dissemination, structural organization, and impact on antibiotic resistance, but do not relate to the antibody clone MECA-89.

The most relevant and authoritative findings pertain to the immunological use of clone MECA-89 as an anti-MAdCAM-1 monoclonal antibody in mouse models to study lymphocyte trafficking and mucosal vascular biology.

Dosing Regimens of Clone MECA-89 Across Different Mouse Models

Overview

The dosing regimens for the anti-MAdCAM-1 antibody clone MECA-89 in mouse models are not standardized and are determined primarily by the specific disease context, pharmacokinetic (PK) parameters, and intended pharmacodynamic (PD) effects. However, direct, detailed information on MECA-89 dosing schedules in recent literature is sparse, and regimens appear to be highly model-dependent, reflecting differences in experimental goals and disease models.

Factors Influencing Dosing

• Disease Context: The primary disease or condition being modeled (e.g., inflammatory bowel disease, lymphocyte trafficking studies) heavily influences the dose and frequency of administration. Different pathologies may require different levels of target engagement or duration of effect.
• Pharmacokinetics: The PK profile of MECA-89—how the antibody is absorbed, distributed, metabolized, and excreted in mice—will directly affect dosing frequency and amount. For monoclonal antibodies in mice, factors such as target-mediated drug disposition (TMDD), FcRn recycling, and clearance rates are critical.
• Pharmacodynamics: The desired biological effect (e.g., blockade of lymphocyte homing, modulation of inflammation) also dictates dosing. Some studies may aim for continuous target saturation, while others may test intermittent or pulsed dosing.

Comparison to Related Antibodies

While specific MECA-89 regimens are not detailed in the provided literature, data for related anti-MAdCAM-1 clones (e.g., MECA-367) show that typical administration is via intravenous injection at single doses, but exact amounts and schedules are not specified and likely vary by study. This variability is consistent with the broader trend for therapeutic antibodies in mice, where dosing is tailored to the experimental model and endpoints.

General Principles in Mouse Antibody Dosing

• Route of Administration: Intravenous injection is common for achieving rapid and complete systemic exposure.
• Dose Frequency: Depending on the antibody’s half-life and the disease model, dosing may be single or repeated. For antibodies with rapid clearance, multiple doses may be needed to maintain therapeutic levels.
• Model-Specific Adjustments: As seen with other agents, “humanized” dosing regimens in mice are sometimes designed to match plasma exposure profiles seen in humans, especially when translational relevance is a priority. This approach could theoretically be applied to MECA-89, but there is no evidence in the current literature that this has been done.

Summary Table: Key Determinants of MECA-89 Dosing in Mouse Models

Conclusion

Dosing regimens for clone MECA-89 in mouse models are not fixed and must be optimized for each specific experimental context, taking into account disease model, PK/PD characteristics, and the desired biological outcome. There is no universal dosing schedule, and researchers are advised to conduct pilot PK/PD studies to establish appropriate regimens for their particular mouse model and research question.