Lung development and immune status under chronic LPS exposure in rat pups with and without CD26/DPP4 deficiency

Andreas Schmiedl,Michael Stephan,Inga Wagener,Meike Jungen,Stephan Von Hörsten

doi:10.1007/s00441-021-03522-8

Abstract

Dipeptidyl-peptidase IV (CD26), a multifactorial integral type II protein, is expressed in the lungs during development and is involved in inflammation processes. We tested whether daily LPS administration influences the CD26-dependent retardation in morphological lung development and induces alterations in the immune status. Newborn Fischer rats with and without CD26 deficiency were nebulized with 1 µg LPS/2 ml NaCl for 10 min from days postpartum (dpp) 3 to 9. We used stereological methods and fluorescence activated cell sorting (FACS) to determine morphological lung maturation and alterations in the pulmonary leukocyte content on dpp 7, 10, and 14. Daily LPS application did not change the lung volume but resulted in a significant retardation of alveolarization in both substrains proved by significantly lower values of septal surface and volume as well as higher mean free distances in airspaces. Looking at the immune status after LPS exposure compared to controls, a significantly higher percentage of B lymphocytes and decrease of CD4+CD25+ T cells were found in both subtypes, on dpp7 a significantly higher percentage of CD4 T+ cells in CD26+ pups, and a significantly higher percentage of monocytes in CD26− pups. The percentage of T cells was significantly higher in the CD26-deficient group on each dpp. Thus, daily postnatal exposition to low doses of LPS for 1 week resulted in a delay in formation of secondary septa, which remained up to dpp 14 in CD26− pups. The retardation was accompanied by moderate parenchymal inflammation and CD26-dependent changes in the pulmonary immune cell composition.

Highlights

CD26/DPP4, called CD26 in the following, is mainly expressed in kidneys and lungs and is involved in different inflammation processes (Mentlein 1999; Klemann et al.Stephan von Hörsten and Michael Stephan contributed .2016)
Applied LPS resulted in a more pronounced significant increase of body weight in C D26+ pups than in CD26− pups compared to controls only on dpp 7 (Table 3)
The lung body weight ratio was only notably lower noteworthy on dpp 7 compared to controls independent of the substrain (Table 3)

Summary

Introduction

CD26/DPP4, called CD26 in the following, is mainly expressed in kidneys and lungs and is involved in different inflammation processes (Mentlein 1999; Klemann et al.Stephan von Hörsten and Michael Stephan contributed .2016). Adult asthma-induced CD26/DPP4-deficient rats exhibited an attenuated inflammation combined with a reduced influx of regulatory T cells and a reduced upregulation of surfactant proteins (Schmiedl et al 2010). A reduced inflammation with differential expression of surfactant proteins in CD26/DPP4 deficient rats was seen after lipopolysaccharide (LPS) administration (Zientara et al 2019). LPS is the biologically active component and primary recognition element in the wall of gram-negative bacteria (Rossol et al 2011). The activated signal cascade leads to an expression of immunoregulatory genes associated with synthesis and release of pro- and anti-inflammatory cytokines like IL-1, Il-6, Il-8, and Il-10 and tumor necrosis factor α (Martin and Frevert 2005; Takeda et al 2003)

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