Increased expression of HMGB-1 in the skin lesions of erythema toxicum.
At birth, commensal microbes penetrate into the skin of the human newborn, eliciting an acute rash, erythema toxicumn neonatorum. Histologically, the rash is characterized by an upregulation of proinflammatory activity and a local recruitment of immunocytes, including macrophages. High mobility group box chromosomal protein 1, a nuclear and cytosolic protein, is also a pro-inflammatory cytokine released by macrophages in response to microbial stimulation. Here, we reasoned that macrophages but also keratinocytes might upregulate this protein in response to the first colonization and that high mobility group box chromosomal protein 1 might play a role as a proinflammatory mediator in the development and progression of erythema toxicum. Punch biopsy specimens from 1-day-old healthy infants, seven with and four without erythema toxicum were analyzed with indirect immunohistochemistry and two different antihigh mobility group box chromosomal protein 1 antibodies, immunofluorescence, nuclear counterstaining, confocal and immunoelectron imaging. We found relocation of nuclear high mobility group box chromosomal protein 1 into the cytoplasm in keratinocytes and macrophages in erythema toxicum. Cytoplasmatic high mobility group box chromosomal protein 1 was also found in melanocytes and did neither co-locate with lysosomal-associated membrane proteins nor with melanosomes. We speculate that terrestrial adaptation triggers the induction of the endogenous "danger signal" high mobility group box chromosomal protein 1 in the skin of the newborn infant, perhaps in response to the first commensal colonization and that this signal may contribute to alert the immune system and promote a protective immune response.
Marchini
Giovanna
G
Division of Neonatology, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden. giovanna.marchini@karolinska.se <giovanna.marchini@karolinska.se>
Hultenby
Kjell
K
Nelson
Annika
A
Yektaei-Karin
Elham
E
Ståbi
Berit
B
Lonne-Rahm
Solbritt
S
Ulfgren
Ann-Kristin
AK
Brismar
Hjalmar
H
D001419:Bacteria / Q000276:immunology; D001706:Biopsy; D004890:Erythema / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D012867:Skin / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
D024243:HMGB1 Protein; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C497811:LAMP2 protein, human; C093846:early endosome antigen 1